Three new benzaldehydes (1e3) and two new dioxopiperazine alkaloids (4 and 5), along with 23 known constituents, were isolated from Antarctic marine-derived Aspergillus sp. SF-5976. Their structures were determined by spectroscopic and chemical methods. Among them, 20 compounds showed inhibitory effects toward lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 values of 7.3e77.4 mM, while 22 compounds did in BV2 microglia with those of 4.6e72.3 mM. Furthermore, the effects of the newly isolated compounds on LPS-stimulated inducible NO synthase (iNOS) expression were investigated, and 1e3, and 5 inhibited iNOS in RAW 264.7 cells, while 1e5 did in BV2 cells. Also, 1e3 and 5 inhibited LPS-induced prostaglandin E2 production with IC50 values of 9.1 e66.8 mM in RAW 264.7 macrophages by suppressing cyclooxygenase-2 (COX-2), while in BV2 microglia, 1e5 showed activities with those of 2.8e49.4 mM.