Salted fish products are one of desirable, traditional and commercial seafood in Egypt. However, some sulfite-reducing anaerobes do not potentiate health hazard, C. perfringens is one of vigorously causing food poisoning globally. This study investigated the drug susceptibility profile and virulence factors of toxigenic C. perfringens, which was isolated from ninety samples of salted Mugil cephalus (feseikh), sardine, and smoked herring (renga) (thirty samples of each), that were randomly collected from different retailers at Qalubiya governorate. The results revealed isolation of eighteen C. perfringens strains from the examined samples (20%); where, it was detected in 30, 20 and 10% of the examined feseikh, renga and sardine samples, respectively. The eighteen detected isolates appeared to be resistant to 41.7% of the tested antibiotics; where, the major resistance was noted against clindamycin (72.2%), while the lowest resistance level was noted against metronidazole (11.1%). For the determination of the detected isolates' virulence profile, plc, proA and cpe genes were examined; where plc and proA were positively detected in all of the examined five isolates; whereas, cpe was positively detected in 80% out of the examined isolates. In addition, bla and ermB resistance genes were examined; where they were detected in 80% and 100% of the examined isolates, respectively. Based on the results obtained, multi-drug resistance toxigenic C. perfringens was found at a substantial rate in one of Egypt's most popular seafood products, indicating possible harm and health hazards for users of such fish products.