Fecal incontinence is a disabling condition in which the passage of fecal material cannot be controlled. Although the condition is not life-threatening, it can seriously reduce the quality of life of a patient by isolating them from others. Though various surgical treatments are available for moderate to severe symptoms, a bulking agent is a minimally invasive technique that has attracted attention because of its safety and simple treatment process. However, the biocompatibility of bulking agent materials remains a central issue, with their durability questioned because immune responses and/or the circulatory system may remove the bulking agent in vivo. This study investigated a bulking agent composed of polydimethylsiloxane and hyaluronic acid as a microfiller and carrier gel, respectively. To improve the injectability of the bulking agent, the filler size was tuned using a suspension-based fabrication technique. To evade immune responses, the filler surface was treated with a zwitterionic polymer that simultaneously functionalized and stabilized the material interfaces. The resulting bulking agent exhibited good injectability and biocompatibility in vitro, with 58% lower protein adsorption and no cytotoxicity, leading to an improved bulking effect in a preclinical rat model compared with a bulking agent without surface treatment. These results illustrate the promising potential of bulking agents as a therapy for fecal incontinence with reduced foreign body reactions and long-lasting efficacy.