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Abstract PremiseBetter understanding of the relationship between plant specialized metabolism and traditional medicine has the potential to aid in bioprospecting and untangling of cross‐cultural use patterns. However, given the limited information available for metabolites in most plant species, understanding medicinal use–metabolite relationships can be difficult. The order Caryophyllales has a unique pattern of lineages of tyrosine‐ or phenylalanine‐dominated specialized metabolism, represented by mutually exclusive anthocyanin and betalain pigments, making Caryophyllales a compelling system to explore the relationship between medicine and metabolites by using pigment as a proxy for dominant metabolism. MethodsWe compiled a list of medicinal species in select tyrosine‐ or phenylalanine‐dominant families of Caryophyllales (Nepenthaceae, Polygonaceae, Simmondsiaceae, Microteaceae, Caryophyllaceae, Amaranthaceae, Limeaceae, Molluginaceae, Portulacaceae, Cactaceae, and Nyctaginaceae) by searching scientific literature until no new uses were recovered. We then tested for phylogenetic clustering of uses using a “hot nodes” approach. To test potential non‐metabolite drivers of medicinal use, like how often humans encounter a species (apparency), we repeated the analysis using only North American species across the entire order and performed phylogenetic generalized least squares regression (PGLS) with occurrence data from the Global Biodiversity Information Facility (GBIF). ResultsWe hypothesized families with tyrosine‐enriched metabolism would show clustering of different types of medicinal use compared to phenylalanine‐enriched metabolism. Instead, wide‐ranging, apparent clades in Polygonaceae and Amaranthaceae are overrepresented across nearly all types of medicinal use. ConclusionsOur results suggest that apparency is a better predictor of medicinal use than metabolism, although metabolism type may still be a contributing factor.