Sorghum is a potential substitute for corn/wheat in cereal-based extruded products. Despite agronomic advantages and its rich diversity of phenolic compounds, sorghum kafirins group together and form complex with tannins, leading to a low digestibility. Phenolic content/profile by UPLC-ESI-QTOF-MSE and kafirins polymerization by SE-HPLC were evaluated in wholemeal sorghum extrudates; tannin-rich (#SC319) and tannin-free (#BRS330) genotypes with/without turmeric powder. Total phenolic, proantocyanidin and flavonoid contents were strongly correlated with antioxidant capacity (r > 0.9, p < 0.05). Extrusion increased free (+60%) and decreased bound phenolics (−40%) in #SC319, but reduced both (−40%; −90%, respectively) in #BRS330, which presented lower abundance after extrusion. Turmeric addition did not significantly impact antioxidant activity, phenolic content and profile and kafirins profile. Tannins presence/absence impacted phenolic profiles and polymerization of kafirins which appears related to the thermoplastic process. The extrusion improved proteins solubility and can positively enhance their digestibility (phenolic compounds-proteins interactions), making more accessible to proteolysis in sorghum extrudates.