Located in tropical and subtropical region, Taiwan is an island with high algal species diversity. In this study, a number of fungal strains were isolated from marine macroalgae collected from northeastern intertidal zone of Taiwan. Preliminary anti-inflammatory screening has shown that the methanolic extracts of solid fermented products of the red alga Mastophora rosea-derived fungal strain Acremonium sp. NTU492 exhibited significant bioactivity. In an attempt to disclose the active principles from this fungal strain, a series of separation and purification was thus undertaken, which has led to the isolation and characterization of seven compounds including four new peptides, namely acrepeptins A-D (1-4), along with previously reported destruxin B (5), guangomide A (6), and guangomide B (7). Their structures were elucidated by spectroscopic analysis and compared with literatures. Of these, acrepeptins A (1) and C (3) showed markedly inhibitory activities on nitric oxide production in lipopolysaccharide-activated microglial BV-2 cells with IC50 values of 12.0 ± 2.3 and 10.6 ± 4.0 μM, respectively. Furthermore, acrepeptins A (1) and C (3) significantly attenuated the expression of inducible nitric oxide synthase in a concentration-dependent manner (5-40 μM).