Dr Leo Schep from Otago University's National Poisons Centre believes a poisonous wine made from an innocuous-looking plant may have killed Alexander, who built a massive empire before his death in 323 BC.
Some historians believe that Alexander's death was due to natural causes, while others maintain he was secretly murdered at a celebratory banquet.
Schep, who has been researching the toxicological evidence for 10 years, said some of the poisoning theories - including arsenic and strychnine - were laughable.
Researchers said the white-flowered plant, which can be fermented into a poisonous wine, was well-known to the Greeks as a herbal treatment for inducing vomiting.
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They believe it could have accounted for the 12 torturous days that Alexander took to die, speechless and unable to walk.
Other suggested poisons, according to the researchers, would likely have killed him far more quickly.
Schep began looking into the mystery in 2003 when he was approached by a company working on a BBC documentary.
Schep's theory is that Veratrum album could have been fermented as a wine that was given to the leader.
Alexander, who was likely to have been very drunk at the banquet, would have tasted the "very bitter" Veratrum album possibly sweetened with wine.
Researchers said, however, whether Alexander was poisoned still remains a mystery.