Objectives <p>This study aimed to compare the efficacy and safety of perioperative somatostatin versus octreotide in peritoneal carcinomatosis (PC) patients after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).</p> Methods <p>Peritoneal cancer patients treated with CRS + HIPEC were divided into two groups (somatostatin group and octreotide group). The postoperative gastric drainage volume, levels of inflammatory factors, perioperative safety and adverse effects were compared between two groups.</p> Results <p>There were 48 (54.5%) patients in the somatostatin group and 40 (45.4%) in the octreotide group. There was no statistically significant difference in the postoperative gastric drainage volume between two groups. The median time to exhaust and defecation (7 d) was comparable between two groups (3–14 d in the somatostatin group and 4–13 d in the octreotide group). There were significant differences in the serum amylase level on postoperative day 3 (<i>P</i> = 0.044), and white blood cell level and neutrophil percentage at every monitoring time. The serious adverse events (SAEs) were similar and there were no long-term follow-up results between two groups.</p> Conclusions <p>Somatostatin and octreotide analogues appear to decrease the duration of enterocutaneous fistulas, but their application in PC patients after CRS + HIPEC might reduce SAEs.</p>