Postoperative cognitive dysfunction (POCD) is one of the major complications in patients who have undergone surgeries. Reduction of surgery-induced inflammation and perioperative stress responses may prevent the development of POCD. As recent experimental data have suggested, Shenmai and Shenfu injections, two ginseng containing formulations, may improve cognition. We designed this study using aged rats as an experimental model to determine the effect of combined perioperative Shenmai injection and Shenfu injection in preventing the development of POCD and exploring the underlying mechanism of this intervention. Aged rats were randomized into one of the two groups. Rats in the experiment group received preoperative Shenmai injection and postoperative Shenfu injection while those of the control group did not receive this treatment. Study results indicate that the memory and cognitive ability of rats in the experiment group were significantly better than those of the control group at postoperative day 1 as well as at day 3. Plasma levels of neuron-specific enolase (NSE), S-100 [Formula: see text] protein, interleukin-6 (IL-6), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), cortisol (COR), aldosterone (ALD), and adenocorticotropic hormone (ACTH) were significantly lower in the experiment group than in those of the control group (day 1 postoperatively). The plasma level of NSE on postoperative day 3 remained lower in the experimental group than in those of the control group. Our experimental results indicate that preoperative Shenmai and postoperative Shenfu injections facilitate conscious recovery and prevent postoperative cognitive decline. This anti-POCD effect may be a result of minimizing surgery-induced inflammation and reduction of perioperative stress responses by these injections.