Objective The present study was undertaken to identify the serotypes and drug resistance profiles of Salmonella recovered from diarrheal patients in Anhui Province, and provide evidence for the diagnosis and treatment of foodborne diseases caused by Salmonella. Methods From 2015 to 2020,980 Salmonella were collected from 16 Centers for Disease Control and Prevention in Anhui Province. The strains were serotyped, and the drug susceptibility profile was studied by micro-broth dilution method. Results Nine hundred and eighty Salmonella included 82 serotypes with a predominance of Salmonella enteritidis 31.43% (308/980), Salmonella typhimurium 26.22% (257/980), Salmonella agona 7.35% (72/980), Salmonella thompson 6.63% (65/980) and Salmonella london 3.37% (33/980). The highest resistance were ampicillin (AMP), nalidixin (NAL), tetracycline (TET) and ampicillin/sulbactam (AMS), which were 62.35%, 47.96%, 47.86%, 43.16%, respectively. The resistance rates to AMP, AMS, NAL, cefoxitin (CFX), and azithromycin (AZM) showed a significant upward trend (P<0.05). The drug resistance of Salmonella showed different features in different regions. It was worse in the north than the south and central Anhui Province. The multi-drug resistance rate reached 40.41%, and Salmonella typhimurium and Salmonella london were highly resistant to multiple drugs. Conclusion From 2015 to 2020, the predominant Salmonella serotypes of diarrheal patients in Anhui Province were Salmonella enteritidis, Salmonella typhimurium, Salmonella agona, Salmonella thompson and Salmonella london. Drug resistance was serious, and most resistance rate showed an increasing trend from 2015 to 2020. The multiple drug resistance was a serious problem. It is necessary to pay close attention to monitor the resistance of Salmonella in Anhui Province.