<p>The Mayan communities of Yucatán have reported an increasing prevalence of chronic noncommunicable diseases (CNCDs). Several studies indicate that secondary metabolites from Yucatán plant foods could be dietary adjuvants for CNCDs. Bioassay-guided studies could be employed as food technology focused on isolating bioactive metabolites. In this sense, the objective is to propose bioguided-assays as a strategic tool for isolating of secondary metabolites from regional plant-based foods in the Yucatán Peninsula for CNCDs management. A search was made for studies that have isolated bioactive secondary metabolites against CNCDs through bioassay-guided studies. The search was performed using the terms" bioassay-guided" or "guided bioactivity" combined with the scientific names of plant foods consumed in the Mayan region of Yucatán. Bioavailability and clinical effect studies of the metabolites were addressed if available. In total, 23 plant foods have reported metabolites with anticancer, antithrombotic, antidiabetic, antihypertensive, and antioxidant activities. Metabolites with an IC₅₀ less than 100&#xa0;μM can be considered strong agents. Further scientific efforts are required to assess the in vitro effect in animal and clinical models. Local studies are suggested because Yucatán abiotic conditions could favor a higher content of secondary metabolites. Additionally, it is suggested that these metabolites could be added to different food matrices to formulate functional foods as adjuvants against the CNCDs. Bioassay-guided studies represent a valuable approach for obtaining secondary metabolites with therapeutic potential from Mayan foods, aimed at managing CNCDs among the Mayan population.</p>