The study was carried out to assess the effect of variety on polyphenols in cassava leaves and their stability in antioxidant activity before and after gastrointestinal digestion. The results showed that individual and total polyphenols content (TPC) and antioxidant activity of bound, free and bioaccessible polyphenols were significantly (p < 0.05) influenced by variety at harvesting maturity. The bound polyphenols had lower TPC (5.00-19.16 mg GAE/g) than free (39.16-89.61 mg GAE/g) throughout harvesting maturity. The polyphenols were strongly affected after digestion, however, salicylic, syringic and benzoic acids are the most bioaccessible. The free polyphenols of variety IRAD4115 had the highest value of FRAP (35.17 μg TE/g) at 12 months after planting (MAP), while, bound polyphenols showed the lowest DPPH (6.59 μg TE/g, variety EN at 12MAP). The antioxidant activity value evaluated by DPPH method was decreased significantly after gastrointestinal digestion. However, there was no significant difference between antioxidant activity of bioaccessible polyphenols (77.71 μg TE/g) and methanolic polyphenols (79.17 μg TE/g) assessed by FRAP method. These findings showed the stability of antioxidant potential of polyphenols in cassava leaves harvested at different periods after digestion. Thus cassava leaves harvested at appropriate maturity can be used as ingredient of functional food for nutraceutical benefits.