A point-of-care (POC) can be defined as an in vitro diagnostic test that can provide results within minutes. It has gained enormous attention as a promising tool for biomarkers detection and diagnosis, as well as for screening of chronic noncommunicable diseases such as diabetes mellitus. Diabetes mellitus type 2 is one of the metabolic disorders that has grown exponentially in recent years, becoming one of the greatest challenges to health systems. Early detection and accurate diagnosis of this disorder are essential to provide adequate treatments. However, efforts to reduce incidence should remain not only in these stages but in developing continuous monitoring strategies. Diabetes-monitoring tools must be accessible and affordable; thus, POC platforms are attractive, especially paper-based ones. Paper-based POCs are simple and portable, can use different matrixes, do not require highly trained staff, and are less expensive than other platforms. These advantages enhance the viability of its application in low-income countries and hard-to-reach zones. This review aims to present a critical summary of the main components required to create a sensitive and affordable enzymatic paper-based POC, as well as an oriented analysis to highlight the main limitations and challenges of current POC devices for diabetes type 2 monitoring and future research opportunities in the field.