Objective: To explore the relationship between hypotension and cognitive impairment during hemodialysis and the intervention effect of aerobic resistance exercise. Methods: The retrospective analysis of 110 hemodialysis patients was collected from January 2020 to June 2021. All patients were treated with aerobic resistance exercise and were divided into 2 groups according to whether the patients had hypotension, namely the occurrence group (n=31) and non-occurrence group (n=79), the general data of the 2 groups were compared, and independent factors affecting the occurrence of hypotension were analyzed by binary logistic regression. Results: Dialysate temperature, ultrafiltration rate, and Mini-Mental State Examination (MMSE) score in the occurrence group were higher than those in the non-occurrence group (all P<0.05). According to Spearman’s method analysis, hypotension during hemodialysis was positively correlated with dialysate temperature and ultrafiltration rate, and negatively correlated with MMSE score. Binary logistic regression analysis showed that hypotension during hemodialysis was related to ultrefiltration rate, dialysate temperature, and MMSE score. At the same time, the patients’ residual capacity, maximal oxygen uptake, left ventricular ejection fraction, 6-min walking distance, interleukin-6 (IL-6), and C-reaction protein (CRP) after the treatment improved better than those before treatment (all P<0.05), Fatigue Scale-14 (FS-14) score after the treatment was lower than that before the treatment (P<0.05). Conclusion: The incidence of hypotension during hemodialysis is high, and it is related to cognitive impairment. Early aerobic resistance exercise therapy can improve cardiac function and reduce fatigue.