Two new α-methoxy- γ-pyrone analogs, 2-methoxy-3-methyl-5,6-diethyl- γ-pyrone (2) and 2-methoxy-3,5-dimethyl-6-propyl- γ-pyrone (3), together with 2-methoxy-3,5-dimethyl-6-ethyl- γ-pyrone (1), firstly isolated from natural sources, were obtained from the EtOAc-solube extract of the mangrove sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126, under the optimized fermentation conditions. Their structures were elucidated by detailed spectroscopic analysis and by comparison of their spectroscopic data with those reported in the literature. Those α-methoxy-γ-pyrones were evaluated for their acetylcholinesterase inhibitory activity; however, none of them exhibited obvious activity. Moreover, their biosynthetic relationship with piericidins was also discussed.