Three new cyclic peptide-polyketide hybrids (<b>1</b>-<b>3</b>) and two new chaetiacandin-type polyketides (<b>4</b> and <b>5</b>) along with nine known compounds were isolated from cultures of a halophyte-associated fungus, <i>Colletotrichum gloeosporioides</i> JS0417. Spectroscopic analysis revealed that <b>1</b>-<b>3</b> were cyclic depsipeptides where 3,5,11-trihydroxy-2,6-dimethyldodecanoic acid was linked to two amino acids through amide and ester bonds to form a 12-membered ring. Relative and absolute configurations for the peptides were determined with spectroscopic analysis and chemical reactions. The cyclic depsipeptides <b>2</b> and <b>6</b> were determined to act as strong adiponectin-secretion-promoting modulators with potential to treat metabolic diseases associated with hypoadiponectinemia. Notably, a known compound, tryptophol, significantly inhibited PGE<sub>2</sub> synthesis and also promoted adiponectin secretion, exhibiting a similar biological activity profile to aspirin, but with greater potency. The presence of an isoleucine moiety and non-glycosylation may be important for biological activity of the cyclic peptide-polyketide hybrids, and non-methoxylation of the side chain may influence activity of the indole derivatives.