Someone comes to PLAYER specifically and asks her to help their kingdom. Their king is extremely sick. PLAYER accepts and they go Koroni Kingdom. The kings symptoms are, weakness, headache, restlessness. 

The town medic has dealt with some of these symptoms, but not all. He says that ore seed can reduce headache, but should not be crushed up, as it voids the effect. It also reacts badly with Ue. Ue is a leaf that makes the body stronger and less weak, but can actually start headache 80 percent of the time. And, now, for the Kue-lele root. It fixes restlessness, but conflicts with ue and Ore.

How do I make this puzzle better and so its challenging? I still want the clashing ingredients and sick king parts, but make it simple but challenging.

Tell the king to STOP TAKING:

Ore Seeds, Ule, and Kue-lel.

He is clearly taking all of those medications

Have a think about what actions you’re players can take and how it works within the context of a D&D game - at first glance I will be honest it doesn’t seem like a great puzzle because 

1) if they have a lesser restoration spell of better why would they not cast that on the king?

2) what are they going to do to solve it, make a medicine check to begin vaccine trials, with a deception check if you want a placebo group.

3) it’s either going to be a quick and inconsequential solve of a long and tedious one.

so let’s rework it - 

key ideas - Sick King, conflicting ingredients, non combat

So what if the king is being poisoned instead of being sick, so instead of finding a cure they have to find the poison, the methodology and the culprit.

first off the players have to figure out he is being poisoned and not sick, he is the only one with symptoms, secondly they have to be unable to cure it through magic or magic item. 

1) hurdle one the kings symptoms don’t match any poison the royal medic has details on

2) hurdle two the kings food and wine have all been tested and no tasters have been getting sick so you know it’s not something he us consuming

twist - he is actually being poisoned from 3 different sources, due to 3 different plans coincidentally being done at the same time

conflicting poisons - this is why he is sick and not dead each poison ingredient is has a side effect that counters the effects of the other in a Rock Paper Scissors fashion. So maybe they find one and the king gets worse when they stop it, but they need to have anti toxins for all 3 to solve it

intrigue - how is he being poisoned? Maybe it’s in the candle wax and he is breathing it in, maybe his quill has been laced with a poison so he has taken it in through touch, maybe it was a poisoned bar of soap, poisoned perfume, poisoned paint used in his bedroom etc

so now finding the cure is also about finding the culprit, finding the methodology, discovering the motive etc

Ooh, so to get him better you need to get him sick. Ill take all this advice and respond again when I rewrite my problem.

sardonicmonkey

Is this good? Dharya is one of my players character, shes a druid firbolg.

Someone comes to dharya specifically and asks her to help their kingdom. Their king is extremely sick. DHarya accepts and they go Koroni Kingdom. The kings symptoms are, weakness, headache, restlessness. 

The town medic has never dealt with these symptoms all at once.The town detective says that it has to be a poisoning. But the only things that can poison. Weve also inspected his wine and food, it has not been poisoned. So its nothing consumed.

You eventually figure out that all the ways to poison someone. You try them on 4 frogs.

You use kue lele root. It makes the frog very weak. Then you try ue, which tires the frog extremely. And ore seed caused the frog an extreme headache, you could hear his brain pulsing. You repoisin the first frog with ore seed. It becomes less weak, but more headachy. 

After some testing, you figure out that ore reduces weakness, and increases headache. Kue lele reduces headache, and increases restlessness. Ue increases restlessness, and decreases weakness. You find a crystal water. You add it to the complete frog, or the frog poisoned by everything. You feed it the crystal water, and it reduces restlessness and weakness. After that you give it some more, the second time, it increases headache. Then, you give it 3 ue leaves, and its no longer headachy, but it has become restless. You use the crystal water again, and its no less restless. You use it again, and it becomes restless no longer, but adds some headache. You give him more ue, he becomes restless but not headachy, then you give him crystal water. Hes all healed. The twist is that, crystal water increases headache the second, fourth, sixth, 8th, Etc time.

Crystal, crystal, ue, ue, ue, crystal, crystal, ue, crystal.

1, 2,1,2,1

You go to the king and explain all that and cure him. (insert finding criminals)

I feel really really proud of this puzzle, but its all because of you. Thanks man!