Effects of two foods with bioactive constituents (black tea brew, BTB and grape seed powder, GSP) on lipid digestibility was studied. Lipolysis inhibitory effect of these foods was examined using two test foods (cream and baked beef) with highly different fatty acid (FA) composition. Digestion simulations were performed either using both gastric and pancreatic lipase, or only with pancreatic lipase according to the Infogest protocol. Lipid digestibility was assessed based on the bioaccessible FAs. Results showed the triacylglycerols containing short- and medium-chain FAs (SCFA and MCFA) are non-preferred substrates for pancreatic lipase; however, this is not characteristic for GL. Our findings suggest that both GSP and BTB primarily affect the lipolysis of SCFAs and MCFAs, because the dispreference of pancreatic lipase towards these substrates was further enhanced as a result of co-digestion. Interestingly, GSP and BTB similarly resulted in significant decrease in lipolysis for cream (containing milk fat having a diverse FA profile), whereas they were ineffective in influencing the digestion of beef fat, having simpler FA profile. It highlights that the characteristics of the dietary fat source of a meal can be a key determinant on the observed extent of lipolysis when co-digested with foods with bioactive constituents.