Anastomotic leakage and postoperative adhesions represent major complications after colorectal surgery. We have previously shown a positive effect on both anastomotic strength and abdominal adhesions by the use of differently charged bioactive polypeptides. The present study aimed to investigate the effect of the same polypeptides on the healing of an insufficient intestinal anastomosis, as well as on accidental intestinal injury, in addition to measuring the preventive effect against the development of abdominal adhesions. An insufficient, and thereby potentially leaking, intestinal anastomosis and punctures of the intestine ("accidental intestinal injury model") were performed in rats. The treatment groups received intraperitoneal administration of poly-L-lysine and poly-L-glutamate, while controls received sodium chloride. Burst pressure, extent of abdominal adhesions, and postoperative complications were analyzed in both experimental models. A significant decrease of adhesions was seen in all animals treated with polypeptides (p < .05). Burst pressure was significantly higher (p < .001) in animals with intestinal perforation as seen on day 1 and then decreasing. A significant decrease in the incidence of peritonitis was also noted early (day 1) in this model (p = .002). The mortality and complications were high in the intestinal anastomosis model, though not affected by treatment with polypeptides. Intraabdominal adhesions were significantly reduced using polypeptides in this study, with no observed effect on other postsurgical complications. There were signs of less infectious complications in polypeptide treated animals. In animals with accidental intestinal injury, a higher burst pressure was noted in treated animals.