In-situ mullite toughened 3Y-TZP composite ceramic (mullite/3Y-TZP) with excellent mechanical properties was fabricated by gel-casting. The cytotoxicity of mullite/3Y-TZP was determined by both extract and direct contact methods, and the results indicated that mullite/3Y-TZP had no acute cytotoxicity. Furthermore, the tribological properties of the tooth enamel sliding against mullite/3Y-TZP in artificial saliva were investigated by using the pin-on-plate friction method. The friction coefficient (μ) between the two friction samples was about 0.464 with a stable friction process, and both of them showed slight wear. Analysis of the wear surface and debris demonstrated that the tooth enamel mainly suffered from fatigue wear accompanied by mild adhesive wear, while mullite/3Y-TZP showed slight abrasive wear. This result indicated that mullite/3Y-TZP had good wear resistance and showed potential applications in dental material.