Microbial-derived natural products provide unique bioactivities and serve as a unique source of drug leads. In the present study, we isolated one new chresdihydrochalcone (1), one new chresphenylacetone (2), and one known streptimidone (3) from Streptomyces chrestomyceticus BCC 24770 using antibacterial activity-guided isolation and purification procedures. We determined their molecular weights using MS and HRMS and elucidated their chemical structures from their 1D and 2D NMR and electronic circular dichroism (ECD) spectra. Compound 1 showed moderate inhibitory activities against the Gram-positive bacteria Methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus. Cytotoxicity and hemolytic activity were not observed at a concentration of up to 100 μg ml-1. The specific antimicrobial activity and low toxicity of compound 1 indicate this compound to be a potential antibiotic candidate, especially as antibiotic resistance has become a significant public health threat.