For thousands of years, traditional natural medicine has been well documented to have low toxicity and good curative effects; however, the bioactive molecules and molecular mechanisms are unclear in many cases due to the difficulties in identifying pharmacodynamic molecules. Here, we report the successful identification of a novel active molecule, CPB13, with antiapoptotic functions from a natural drug (Colla corii asini, CCA) by combining phenotypic screening with proteomics approaches. Functional studies in cell and animal models demonstrated that the molecule CBP13 improves the morphology and functions of mitochondria in a dose-dependent manner and inhibits mitochondrial protein reduction and apoptosome activity. Molecular modeling and docking analysis revealed that CBP13 prefers a concave conformation, which can potentially bind to human cytochrome C and Apaf-1, providing hints regarding the molecular basis by which CBP13 inhibits the apoptosis signaling cascade. The results indicate that CBP13 can be developed into drugs that regulate apoptosis, providing a new avenue for antiaging and anti-inflammatory applications.