Objective: Drug dependence has become a major global public health problem. This study aimed to investigate the effects of moderate-intensity aerobic exercise on the blood-brain barrier and neurological damage in methamphetamine (MA)-dependent individuals. Methods: MA-dependent individuals (all males) were recruited and randomly divided into MA exercise group (MAE) and MA control group (MAC) by using random number table method. The MAE group underwent 12 weeks of moderate-intensity aerobic exercise, and the MAC group underwent conventional detoxification. The Neurofilament light chain (NfL), S100 calcium binding protein b (S100b), and Neuron-Specific Enolase (NSE) levels in the blood of MA-dependent individuals were measured before and after the exercise intervention. Results: After the exercise intervention was implemented, the amount of change in NfL in the plasma of the MAE (1.75 +/- 1.40) group was significantly different from that of the MAC (0.60 +/- 1.21) group (p < 0.01); the amount of change in NSE in the serum of the MAE [-1.51 (-3.99 similar to 0.31)] group was significantly different from that of the MAC [0.03 (-1.18 similar to 1.16)] group (p < 0.05); and the amount of change in S100b in the serum of the MAE [0.66 (0.40 similar to 0.95)] group was not significantly different from that of the MAC (0.60 (0.21 similar to 1.04)) group (p > 0.05). Conclusion: This study showed that 12 weeks of moderate-intensity aerobic exercise treatment significantly promoted the recovery of blood-brain barrier and neurological damage in MA-dependent patients compared with conventional withdrawal.