A new isoprenylated flavanone, macahuilettiin A (1), along with lonchocarpol A (2) and nymphaeol C (3), were isolated from Macaranga hullettii King ex Hook leaves. Their structures were combined by UV, high‐resolution ESI‐TOFMS, 1D‐, and 2D‐NMR spectra analysis. Flavanones 1–3 were assayed for antiplasmodial activity toward Plasmodium falciparum 3D7, which was carried out using the Trager and Jansen method, showing that the IC50 values for flavanones 1–3 were 0.15, 1.64, and 0.61 µm, respectively, which is classified as high activity.