Self-cleaning surfaces allow the reversible attachment and detachment of microorganisms which show great promise in regards to their reusability as smart biomaterials. However, a widely used biomaterial such as polydimethylsiloxane (PDMS) suffers from high biofouling activity and hydrophobic recovery that results in decreased efficiency and stability. A current challenge is to modify and fabricate self-cleaning PDMS surfaces by incorporating antifouling and pH-sensitive properties. To address this, we synthesized a zwitterionic and pH-sensitive random poly(glycidyl methacrylate-co-sulfobetaine methacrylate-co-2-(dimethylamino)ethyl methacrylate) polymer, poly(GMA-co-SBMA-co-DMAEMA). In this work, chemical modification of PDMS was done by grafting onto poly(GMA-co-SBMA-co-DMAEMA) after surface activation via UV and ozone for 90 min to ensure the formation of covalent bonds necessary for stable grafting. The PDMS grafted with G20-S40-D40 exhibit antifouling and pH-sensitive properties by mitigating fibrinogen adsorption, blood cell adhesion, and releasing 98% adhered E. coli bacteria after immersion at basic pH. The grafting of poly(GMA-co-SBMA-co-DMAEMA) presented in this work shows attractive potential for biomedical and industrial applications as a simple, smart, and effective method for the modification of PDMS interfaces.