The commonly used “stealth material” poly(ethylene glycol) (PEG) effectively promotes the pharmacokinetics of therapeutic cargos while reducing their immune response. However, recent studies have suggested that PEG could induce adverse reactions, including the emergence of anti‐PEG antibodies and tissue histologic changes. An alternative stealth material with no or less immunogenicity and organ toxicity is thus urgently needed. We designed a polypeptide with high zwitterion density (PepCB) as a stealth material for therapeutics. Neither tissue histological changes in liver, kidney, or spleen, nor abnormal behavior, sickness or death was induced by the synthesized polymer after high‐dosage administration for three months in rats. When conjugated to a therapeutic protein uricase, the uricase–PepCB bioconjugate showed significantly improved pharmacokinetics and immunological properties compared with uricase–PEG conjugates. Stealth material: A zwitterionic polypeptide (PepCB) was synthesized and conjugated to therapeutics as a stealth material. PepCB exhibited superior biocompatibility and non‐immunogenicity in animal experiments compared to poly(ethylene glycol) (PEG). The new material holds great potential as a PEG alternative for formulating safer and more effective therapeutics.