Management of type-II diabetes through regulating the activity of alpha-glucosidase is a promising therapeutic approach. Here, bioassay-guided isolation of algal secondary metabolites (ASM) from microalgae (Chlorella minutissima) inhibiting alpha-glucosidase was explored. In this study, the purified column fractions (SIV-P2) of C. minutissima acetone extract obtained from flash chromatography exhibited alpha-glucosidase inhibition potential with the IC50 value of 1.61 mg mL-1, and the active fractions were dominated by terpenoids and alkaloids. Further, molecular dynamics simulations revealed that Lucidine B, an alkaloid compound possesses the least binding energy (BE) of-318 KJ mol-1 when compared to the standard drug acarbose (-216.781 KJ mol-1). Lucidine B formed a hydrogen bond with Glu408 which possibly induced cleft closure and prevented the sub-strate entry to the active site (non-competitive inhibition). The present study unveils that ASM could be exploited as a potential inhibitor of alpha-glucosidase and may be used for the alleviation of type-II diabetes.