The leaves of Piper auritum Kunth (‘Hoja Santa’) have been consumed for centuries by native people of central and southern Mexico as a fresh vegetable or condiment. Herein we present the result of the 1H‐NMR metabolomics profiling of three accessions of P. auritum harvested in three different provinces of Mexico (Puebla, Tlaxcala, and Oaxaca). The volatile content associated with the flavoring properties of the plant was also determined by GC/MS. The non‐targeted metabolome of these samples revealed that P. auritum is a source of free essential amino acids such as isoleucine, leucine, threonine, valine, histidine, phenylalanine, and tryptophan as well as organic acids, free monosaccharides, and valuable nutraceuticals such as trigonelline, Myo‐inositol, betaine, and choline. Principal component analysis and orthogonal partial least squares discriminated analysis of the metabolites found in P. auritum revealed trigonelline as the main differential compound found in the three studied accessions, suggesting this metabolite as a possible chemical marker. According to these statistical approaches, 60 % of the differential metabolites were provided by Oaxaca samples, suggesting that leaves harvested in this province have better (p<0.05) nutritional properties than the other samples analyzed. Nevertheless, the high abundance of the anti‐nutrient safrole (90 %) in the volatile fraction, advises the potential toxicity of P. auritum consumed in Oaxaca. On the other hand, samples harvested in the northern highlands of Puebla, contained the lowest levels of safrole (30 %) and acceptable levels of nutrients and nutraceuticals including choline. From the three groups of studied plants, those harvested in the northern highlands from Puebla, could be considered safer for human consumption than the other analyzed accessions.