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Zinc (Zn)–dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn–Dy alloys with tailored proper bio‐mechanical and osteointegration properties for bone regeneration. A Zn‐5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn‐5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn‐5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4‐mediated mitochondrial function. In vivo Micro‐CT, SEM‐EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn‐5Dy alloy during bone healing, which also depends on the upregulation of SIRT4‐mediated mitochondrial events. Overall, the study is the first to report a Zn‐5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria‐targeting materials in enhancing bone fracture healing. [ABSTRACT FROM AUTHOR]