Biopolymeric films have been the focus of research for the past few decades because they offer favorable advantages compared to synthetic polymeric films in the field of biomedical engineering. In this study, collagen (C) was extracted from skin waste using acetic acid and blended with starch (ST)/soy protein (SP) to prepare C/ST/SP hybrid films. The prepared hybrid films were examined for biocompatibility, physical and chemical properties. The results demonstrated that the strength properties of hybrid films increase as the composition of starch increases while elongation increases as the composition of soy protein increases. Thermogravimetric analysis of select hybrid films showed that the thermal stability of the hybrid films improved moderately. The infrared spectroscopy of hybrid films show functional groups associated with C, ST and SP. Scanning electron microscopy reveals that the hybrid films becomes smoother as the starch concentration increases while increasing soy protein concentration lead to roughness in the hybrid films. The equilibrium swelling, in vitro biodegradation and in vitro cytotoxicity studies show good biostability and biocompatibility for the hybrid films. Therefore, it is envisaged that the promising mechanical, thermal, swelling, biostability and biocompatibility properties of the developed hybrid films suggest a beneficial role for the biomedical applications.