The present study sought to investigate the effect of ripening on the antioxidant properties and phytochemical constituents of plantain, a major staple food of global consumption. This was done by measuring the total phenolics and flavonoid content of both ripe and unripe form of plantain. Moreover, the free radical scavenging, ferric reducing and iron chelating properties of both forms of plantain were also investigated. Finally, the ability of both extracts to prevent pro-oxidant induced deoxyribose degradation and lipid peroxidation in both cerebral and hepatic tissues of rat was also assessed. Results revealed that ripening depleted the total phenolics [(unripe, 16.2 ± 0.75 mg/g (GAE); ripe, 8.3 ± 0.55 mg/g (GAE)] and flavonoid [(unripe, 15.2 ± 0.45 mg/g (QE); ripe, 9.5 ± 0.21 mg/g (QE) content of plantain. Moreover, the unripe plantain extract exhibited a significantly higher free radical scavenging, iron (II) chelating and ferric reducing effect than the ripe extract. Finally, the unripe plantain extract offered a marked inhibitory effect against pro-oxidant induced deoxyribose degradation and lipid peroxidation than the ripe extract. Put together, we could suggest that the observed depletion in antioxidant properties of ripe plantain may be due to an irreversible degradation in the phytochemical constituents of the fruit as ripening progresses. This study would create a public awareness on the effect of ripening on the therapeutic potentials of plantain and serve as useful information in the global fight against degenerative diseases whose etiology has been linked to oxidative stress.