Objective To investigate the therapeutic effect of continuous renal replacement therapy (CRRT) plus hemoperfusion (HP) on patients with diabetes and uremic encephalopathy. Methods Fifty-five patients with diabetes and uremic encephalopathy from January 2010 to December 2017 were retrospectively collected in this study and divided into CRRT plus HP (CRRT+HP) group (n=28) and hemodialysis (HD) plus HP (HD+HP) group (n=27). The changes of vital signs, related biochemical indicators before and after treatment and curative effects were compared between the two groups. Results The two groups were comparable in general. No significant differences were found in blood pressure or heart rate before and after treatment between the two groups (P>0.05). The incidence of hypotension events in CRRT+HP group was significantly lower than that in HD+HP group (P<0.05), and the effective rate of cardiac function improvement in CRRT+HP group was significantly higher than that in HD+HP group (P<0.05). After treatment, the blood urea nitrogen, creatinine, parathyroid hormone, β2-microglobulin, phosphorus, C-reactive protein and brain natriuretic peptide in the two groups were significantly decreased than those before treatment (P<0.05). Parathyroid hormone, β2-microglobulin, C-reactive protein and brain natriuretic peptide were significantly decreased in CRRT+HP group as compared with those in HD+HP group (P<0.05). The remission rate of uremic encephalopathy in CRRT+HP group was significantly higher than that in HD+HP group (P<0.05). Conclusions As compared with HD+HP pattern, CRRT+HP pattern is more stable in the hemodynamics, and more effective in the improvement of heart failure and the clearance of inflammatory mediators, middle molecular and macromolecular substances associated with uremic encephalopathy. CRRT+HP pattern is suitable for the treatment of patients with diabetes and uremic encephalopathy.