Phytochemical analysis of 3 members of the Urticaceae family (eg Pilea pumila, Laportea canadensis, and Boehmeria cylindrica) was conducted using GC-MS. P pumila and L canadensis have several recorded historical medicinal uses by Native American tribes, whereas B cylindrica does not. This study was conducted to understand the historical uses in terms of chemical composition. Plant material, separated into aerial or root portions, was dried and extracted using either ethanol or heptane at room temperature. Sterols, fatty acids and esters, terpenes and terpenoids, saturated and monounsaturated hydrocarbons, small oxygen-functionalized organic molecules, and tocopherols were observed using these methods. Plant sterols composed 30.3% to 62.2% of the observed extracts, followed by fatty acids and esters ranging from 0% to 49% and terpenes and terpenoids ranging 4.56% to 33.9%. All 3 plants contained γ-sitosterol as the dominant plant sterol and palmitic, linoleic, and linolenic acids and esters. The 3 plants differed significantly in the observed terpene and terpenoid composition. Germacrene D-4-ol, known to have antifungal activity, was the major terpenoid identified in P pumila (7.42%-7.76%), phytol (4.13%), α-cadinene (3.96%), and cadina-1,4-diene (5.53%) were observed in L canadensis treatments, and squalene (2.20%-7.04%), phytol (4.17%), and cadina-1,4-diene (6.68%) were observed in B cylindrica treatments . Possible rationales for Native American medicinal uses were evaluated.