TP53, also known as the "guardian of the genome," is an important tumor suppressor gene. It is encoded by the human genome and is associated with the development of diverse cancers. The p53 protein, encoded by TP53, functions in the cell to monitor DNA damage and prompts the cell to respond appropriately. When DNA is damaged, p53 halts the cell cycle, allowing cells to enter the repair state. If the repair is ineffective, p53 induces cell death via apoptosis. This prevents DNA damage transmission during cell division and reduces cancer risk. However, the p53 gene mutation compromises its function. This leads to the inability of cells to respond properly to DNA damage, which may result in cancer development. Mutations in p53 are widespread in diverse cancers, especially highly prevalent cancers, including breast, colon, and lung cancers. Despite the association between p53 mutations and cancer, researchers have discovered drugs and treatments that may reactivate mutated p53 function. Therefore, p53 remains an important area of research in cancer treatment and holds promise as a new direction for cancer therapy. In summary, TP53 is a vital tumor suppressor gene responsible for monitoring DNA damage and prompting cells to respond appropriately. This article summarizes drugs related to p53 and diverse strategies for discovering drugs that act on either wide or mutant p53. Herein, p53 is categorized into two types: wild and mutant type. Drugs are also classified according to diverse treatment strategies, enabling readers to differentiate between the two types of p53 and aiding in selecting the appropriate research direction. Additionally, this review offers a valuable reference for drug design.