This work assessed the effect of lime treatment (nixtamalization) on the reduction of tannins in grain sorghum and on the subsequent enzymatic hydrolysis of the lime-treated flours. A split-plot experimental design for the lime treatment and a factorial experimental design, with variety of sorghum and lime concentration as factors, were used. Sorghum flours were prepared by cooking sorghum grains (low, medium, and high tannins) in lime solutions (0.0%, 0.3%, and 0.5%) for 35 min at 87°C, steeping for 8 hr, washing, drying, and sieving. Lime treatment reduced the tannins content by 82%, 67%, and 53% with 0.3% lime and by 79%, 68%, and 49% with 0.5% lime treatments for high, medium, and low tannins varieties. Hydrolysis with α-amylase and amyloglucosidase showed that sorghum variety, lime concentration, and their interaction were highly significant in the production of fermentable sugars (p < 0.001). Conversion efficiency of starch into fermentable sugars increased with rising concentrations of lime. Practical applications The present study demonstrated that lime-pretreatment (nixtamalization) of sorghum grain effectively reduce the polyphenols content in grain sorghum, particularly condensed tannins. Subsequently, the reduction of polyphenols improves the conversion of starch into fermentable sugars, which is highly beneficial in industrial fermentations.