In this work, a series of CoCrFeNiCe (x = 0.1, 0.3, 0.5) high-entropy alloys (HEAs) were designed and prepared through vacuum induction melting. The microstructure, wear resistance and antibacterial behaviors of the HEAs were systematically investigated. The results showed that the HEAs are composed of FCC phase with dendrite structure and CeNi phase between dendrites. With the increase of Ce content, the mechanical property and antibacterial rate of the alloys was improved gradually. Due to the combined effect of CeNi phase and fine grain strengthening, the CoCrFeNiCe HEA exhibited high hardness of approximately 382 HV and the wear rate of only 1.11 × 10 mm/N·m under the loading force of 5 N. The CoCrFeNiCe HEA also showed excellent antibacterial ability, which presented a 97.4% antibacterial rate against Escherichia coli and 89.6% antibacterial rate against Staphylococcus aureus after 3 days. This work provided a new strategy for designing a high performance alloy with excellent antibacterial behaviors and good wear resistance, which makes it meet the needs of long-term antibacterial application in harsh environments.