Background Although laparoscopic appendectomy (LA) is considered to be minimally invasive compared with open appendectomy (OA), there are few studies showing this in terms of cytokines and oxidative stress markers. Aim LA and OA techniques have been compared in terms of different conditions such as operation time and complication rate. Here, we compared how oxidative DNA damage and some cytokines levels change in relation to LA and OA. Method This study was performed in children diagnosed with acute appendicitis in our hospital. The study was conducted on 30 children with acute appendicitis in each group. Oxidative DNA damage and malondialdehyde levels were determined by high-performance liquid chromatography, and interleukin-1 beta, interleukin-37, ischaemia-modified albumin and total thiol levels were determined by enzyme-linked immunosorbent assays. Results There was a dramatic decrease in ischaemia-modified albumin (IMA) levels after LA. However, there were no statistically significant differences in pre- and postoperative IMA levels in the OA group. Oxidative DNA damage and malondialdehyde levels were low significantly according to preoperative levels after the LA and OA. Total thiol levels were high in children who underwent LA while they were low after OA. In addition, postoperative interleukin-1 beta levels were low in both groups. Furthermore, IL-37 levels postoperatively were low in the LA group, while there was no significant change in the OA group. Conclusion LA had a more positive effect on oxidative DNA damage, IL-1 beta and IL-37 than the OA. In addition, surgical stress was reduced with LA.