Objective To examine the anti-central-fatigue function of maca and its underlying mechanism. Methods Forty Sprague-Dawley rats were divided randomly into a negative control group, model control group, and low-, medium-, and high-dose maca groups (0.6, 1.2, and 2.4 g/kg·body weight). Rats in all groups except the negative control group were subjected to multi-factor stimulation, including cold-water swimming, sleep deprivation, restraining, and tail-clamping, to establish central fatigue rat models. Rats in the low-, medium-, and high-dose maca groups received 0.6, 1.2, or 2.4 g/kg maca, respectively, by gavage for 35 days. Behavioral testing was carried out using the Morris water-maze, sucrose-preference, and tail-suspension tests. Markers of oxidative stress in the hippocampus, including superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT), were detected using test kits. Proteins connected with the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/ peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) signaling pathway in the hippocampus were detected by Western blot. Results Rats in the low-, medium-, and high-dose maca groups spent significantly more time in the target quadrant compared with the model control group (P<0.05 or P<0.01), but there was no significant dose-effect relationship. Rats in the medium- and high-dose maca groups showed decreased escape latency (P<0.05), increased time crossing the platform location (P<0.05), increased sucrose preference (P<0.05), decreased tail suspension time (P<0.05), increased the activities of CAT (P<0.01) and SOD (P<0.05), and decreased MDA content (P<0.01). Rats in the low-, medium-, and high-dose maca groups also showed significantly increased protein expression levels of AMPK and nuclear respiratory factor 1 (P<0.01 or P<0.05), but no significant dose effect relationship was observed. Rats in the medium- and high-dose maca groups showed increased protein expression of PGC-1α (P<0.05 or P<0.01), and rats in the high-dose maca group showed increased protein expression of SIRT1 and mitochondrial transcription factor A (P<0.05 or P<0.01). Conclusions Maca can improve the indicators of central fatigue in rats, determined by behavioral testing and oxidative stress-related factors. The underlying mechanism may be related to its regulatory effects on the AMPK/SIRT1/PGC-1α signaling pathway.