Lentinus edodes (SM) are highly appreciated by the food industry together with consumers for nutrition and flavour. It is hypothesized the results of our study can indicate to the suitable cooking method for maximal nutrient retention, this study investigated the effects of six cooking methods on the proximate composition, digestive properties, and antioxidant activities of SM in vitro simulated digestion. The results revealed that the ash and protein contents of cooked samples were reduced excluding steaming and roasting, and likewise minerals during deep-frying and boiling (e.g., Mg from 1080.07 to 629.03 mg/kg, deep-frying). A conspicuous rise in fat and energy was found in deep-frying and stir-frying. Steaming retained more reducing sugar (3.80 mg/mL). Roasting improved bioaccessibility of most amino acids (e.g., 82.61%, Asp). Using oil as a medium was associated with higher antioxidant activities using water. Steaming and roasting were better for preserving the nutrient composition of cooked Lentinus edodes.