The effect of crude and nanoencapsulated extracts of cuachalalate (Amphipterygium adstringens) bark extracted in ethanol and cancerin (Hippocratea excelsa) extracted in petroleum ether, on human peripheral blood mononuclear cells (PBMC), was evaluated. The extraction of secondary metabolites from the plants was obtained by maceration for 24 h in the indicated solvents. The evaluated concentrations of the extracts on the (PBMC) were 0.01–1000 mg/mL. The Amphipterygium adstringens extract in ethanol affected cell viability from 10 mg/mL, and the Hippocratea excelsa extract in petroleum ether presented greater cytotoxicity in the cells, decreasing viability from 0.1 mg/mL. The extracts were nano-encapsulated in a polymer matrix composed of pectin and whey, obtaining spherical nanocapsules. Scanning Electron Microscopy (SEM) analysis revealed that the nanocapsules had sizes smaller than 600 nm. The nanoencapsulated extract Hippocratea excelsa in petroleum ether showed an immunomodulatory effect on mononuclear cells, observing an increase in cell viability of more than 100%, at concentrations of 100 mg/mL, compared to the control.