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Recent research indicates that Photoplethysmography (PPG) signals carry more information than oxygen saturation level (SpO2) and can be utilized for affordable, fast, and noninvasive healthcare applications. All these encourage the researchers to estimate its feasibility as an alternative to many expansive, time-wasting, and invasive methods. This systematic review discusses the current literature on diagnostic features of PPG signal and their applications that might present a potential venue to be adapted into many health and fitness aspects of human life. The research methodology is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2020. To this aim, papers from 1981 to date are reviewed and categorized in terms of the healthcare application domain. Along with consolidated research areas, recent topics that are growing in popularity are also discovered. We also highlight the potential impact of using PPG signals on an individual’s quality of life and public health. The state-of-the-art studies suggest that in the years to come PPG wearables will become pervasive in many fields of medical practices, and the main domains include cardiology, respiratory, neurology, and fitness. Main operation challenges, including performance and robustness obstacles, are identified.