The aim of the study was to determine the feasibility of the Vitellaria paradoxa nutshell as a new medicinal resource for treating diabetes.A total of forty-one compounds were identified by HPLC-DAD-Q-TOF-MS and phytochemical methods in V.paradoxa nutshell methanol extract.Based on HPLC fingerprints,four characteristic constituents were quantified and the origin of twenty-eight V.paradoxa nutshells from seven sub-Saharan countries was compared,which were classified into three groups with chemometric method.Twenty-eight samples contained high total phenolic content,and exhibited moderate-higher antioxidant activity and strong α-glucosidase inhibitory activity.Furthermore,all fractions and isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities,and α-glucosidase inhibitory action mechanism of four characteristic constituents including protocatechuic acid,3,5,7-trihydroxycoumarin,(2R,3R)-(+)-taxifolin and quercetin was investigated via molecular docking method,which were all stabilized by hydrogen bonds with α-glucosidase.The study provided an effective approach to waste utilization of V.paradoxa nutshell,which would help to resolve waste environmental pollution and provide a basis for developing potential herbal resource for treating diabetes.