Horsfieldia macrobotrys Merr has long been used by Dayak people in East Kalimantan of Indonesia, for diabetes therapy. Inspired by ethnopharmacological use and promising α-glucosidase and radical scavenging activities, an attempt to identify the active components was carried out. Bioassay-guided isolation yielded two related arylalkanones named 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one (1) and malabaricone A (2). Arylalkanone 1 showed potent radical scavenging comparable with that of the standard antioxidant, ascorbic acid, and promising inhibition against α-glucosidases. Noticeably, arylalkanone 1 was 3-30 times more potent than malabaricone A (2) in all bioassays examined, thus suggesting the critical role in exerting bioactivities of the hydroxy group on the aryl moiety. This hypothesis was also supported by reduction in inhibitory effects of the methyl ether analogues la and 2a. Arylalkanone 1 inhibited yeast α-glucosidase in a mixed-type manner in which the noncompetitive pathway was dominant over competitive inhibition. This study is the first report of α-glucosidase inhibition of arylalkenone-type compounds and the first phytochemicals from H. macrobotrys.