•Ovatifolionone acetate showed a good degree of COX-2 selectivity.•Five compounds were isolated from Ledebouria socialis and L. ovatifolia.•Compounds isolated showed COX-1 and COX-2 activity.•Circular dichroism was used to establish absolute configurations.The bulbs of Ledebouria socialis (Hyacinthaceae) yielded the benzocyclobutene homoisoflavonoid, (R)-2′,5-dihydroxy-3′,4′,7-trimethoxyspiro{2H-1-benzopyran-3-(4H)-9-bicyclo[4.2.0]octa[1,3,5]triene}-4-one, socialinone (1). Ledebouria ovatifolia yielded (2ε,3R)-2,5-dihydroxy-7-methoxyspiro[2H-1-benzopyran-3(4H), 5′(6′H)-cyclobuta[f][1,3]benzodioxol]-4-one (2) and the homoisoflavanone, (E)-3-(3′,4′-dihydroxybenzylidene)-5,7-dihydroxychroman-4-one, ovatifolionone (5), the dihydrochalcone, 4,4′-dihydroxy-2′,6′-dimethoxydihydrochalcone (3), and xanthone, 1,6-dihydroxy-2,3,5-trimethoxy-8-methyl-9H-xanthen-9-one (4) along with 21 known compounds. Structures were determined using spectroscopic techniques. The anti-inflammatory activities of the homoisoflavonoids and xanthones isolated were evaluated against cyclooxygenase-1 and -2 isoenzymes. (R)-3-(3′,4′-Dihydroxybenzyl)-7-hydroxy-5-methoxychroman-4-one (7), (E)-3-(3′,4′-dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one (10), 1,3,6-trihydroxy-2-methoxy-8-methylxanthen-9-one (6) and ovatifolionone acetate (5Ac) exhibited significant activity against cyclooxygenase-2 at <10 μM.Homoisoflavonoids, including (E)-3-(3′,4′-dihydroxybenzylidene)-5-acetoxy-7-hydroxychroman-4-one (ovatifolionone acetate) and (E)-3-(3′,4′-dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one, showed selective COX-2 inhibition.