Sesame seeds (Sesamum indicum) were processed into flour using defatting, cooking, roasting, germination and fermentation processing methods. The processed sesame seed flour (SSF) was used at four substitution levels of 5, 10, 15 and 20% to wheat flour (WF) to produce cookies. Thereafter, the effects of the five processing methods on the total nitrogen, soluble nitrogen and in-vitro protein digestibility of the produced cookies were studied. The result of the study revealed that substitution of wheat with 20% roasted, defatted and cooked sesame seed flours gave total nitrogen content of 2.15, 2.09 and 1.90%, respectively. Increasing substitution level of defatted, cooked and fermented SSF to WF led to decreasing in-vitro protein digestibility values of the cookies from 61.36 to 30.75%, 37.21 to 32.98% and 63.28 to 32.99%, respectively. While increasing substitution levels of wheat flour with germinated sesame seed flour was observed to increased the in-vitro protein digestibility of the cookies from 34.82 to 51.39%. In terms of the roasted SSF, 10% substitution level to WF had the highest in-vitro protein digestibility value of 52.27% while decreasing values (43.55 to 27.38%) were recorded from 15 to 20% substitution levels, respectively. In-vitro protein digestibility of cookies produced from wheat in composite with processed sesame seed flour was significantly (P<0.05) higher than that of the control (100% wheat flour cookies). Hence, sesame seeds can be processed into flour via the studied processing methods and used in substitution to wheat in the production of cookies to improve its protein digestibility.