Alpha-fetoprotein (AFP) is a glycoprotein mainly produced during fetal development, and elevated levels in adults are frequently associated with liver diseases, especially hepatocellular carcinoma (HCC), as well as certain germ cell tumors. Measuring AFP in biological samples is crucial for early diagnosis, monitoring disease progression, and evaluating treatment efficacy. While traditional detection methods like enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay are dependable, they often face limitations such as lengthy processes, complexity, and the need for specialized equipment. In recent years, biosensing technologies have emerged as promising alternatives for detecting AFP, offering advantages like increased sensitivity, real-time monitoring, and ease of use. Various biosensing platforms, including electrochemical, optical, and piezoelectric sensors, have been developed to enable quick and specific detection of AFP. These sensors employ molecular recognition elements, such as antibodies, aptamers, or nanoparticles, to selectively bind AFP, producing a measurable signal. This article explores the structure and mechanisms of action of AFP, the diseases linked to it, and describes several biosensing technologies. It also reviews recent advancements in AFP biosensing, discussing their principles, performance, and potential applications in clinical settings. Furthermore, the article highlights the challenges and future prospects for developing cost-effective, portable, and multiplexed AFP biosensors, underscoring their potential to revolutionize early disease detection and personalized healthcare.