Digestive enzymes secreted by the body are vital for digestion and nutrient absorption. Enzyme supplements are commonly used to support them in achieving optimal digestion. Herein, the efficacy of digestive enzyme supplement (DigeSEB Super) in digestion of complex food was assessed using INFOGEST simulated static and modified semi-dynamic digestion models. Digestive enzyme supplement was found to assist the endogenous digestive enzymes to disintegrate the food matrix. Hence, it reduced the viscosity of the gastric digesta by 2.75 fold ( = 0.04) compared to the control digestion (only endogenous digestive enzymes) during the first hour of digestion. Similarly, enzyme supplement showed statistically higher release of reducing sugars in the gastric digestion ( ≤ 0.05) indicating improved digestion of carbohydrates. Further, digestion of proteins and fats was also improved in the presence of enzyme supplement. The kinetic aspects of the semi-dynamic model (transient nature of gastric secretions and gradual acidification) was found to alter the macronutrient digestion compared to the static digestion. Thus, semi-dynamic model should be preferred for the studies. Overall, current study demonstrated the potential of a digestive enzyme supplement to improve digestion by aiding digestive action of the endogenous enzymes.