The superhydrophilic and ultralow biofouling properties as well as the resistance to foreign-body reaction make zwitterionic polymer promising in biomedical applications. Incorporation of arginine–glycine–aspartate (RGD) sequence and/or vascular endothelial growth factor mimicking (QK) peptide to zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels may not only improve cell adhesion but also influence stem cell differentiation. In this study, PSBMA hydrogels were modified with RGD or RGD/QK peptides and characterized. Multipotent human adipose-tissue derived stem cells (hASCs) were seeded to peptides-grafted PSBMA hydrogels, and the cell adhesion, proliferentiation, and differentiation of hASCs on hydrogels were demonstrated. The results showed that grafting of RGD or RGD/QK peptides improved hASCs adhesion, while the mechanical strength of peptides-grafted PSBMA hydrogels was decreased. Incorporation of RGD or RGD/QK peptides did not influence the adsorption adsorption behaviors of PSBMA hydrogels. Relative to RGD-grafted PSBMA hydrogels, the RGD/QK incorporation further improved hASCs differentiated into adipogenic lineage, while RGD or RGD/QK additions had no substantial effects on osteogenesis under osteogenic induction. Moreover, the endothelial differentiation was also enhanced when hASCs cultured on RGD/QK-modified PSBMA hydrogels. In conclusion, the graftings of RGD and RGD/QK did not interfere the nonfouling property of PSBMA hydrogels. The incorporation of RGD/QK peptides can improve hASCs differentiate toward adipogenic/endothelial lineages.