This systematic review aims to synthesize the data on the effectiveness of pharmacological modulation of stress response in minimally invasive surgery. Eligible trials were clinical trials randomized or not or experimental trials that investigated the effect of pharmacological agents on modulation of surgical stress response to minimally invasive surgery. No clinical trials were identified. Eight experimental trials met the inclusion criteria and were obtained in full text. Experimental models were rats or rabbits subjected to pneumoperitoneum, or pneumoretroperitoneum, not to a whole operation. Pharmacological modulation of surgical stress response was attempted with erythromycin, melatonin, mesna, verapamil, pentoxifylline, N-acetylcysteine, and zinc. All the pharmacological agents, except pentoxifylline, seemed to reduce oxidative stress markers. However, only mesna pretreatment prevented oxidative stress, because oxidative stress markers remained in the sham levels. Contrasting data were obtained for pentoxyphilline. In conclusion, available data suggest that pharmacological modulation of surgical stress response to minimally invasive surgery might be feasible.