Immunosuppressive activity guided chemical investigation, four alkaloids (1–4) and eight polyketides (5–12) were isolated from mangrove-derived Aspergillus fumigatus HQD24. Their structures were elucidated unambiguously based on the comprehensive spectroscopic analysis and comparison with literature data. Compounds 1 and 3–5 were separated from mangrove endophytic fungi for the first time, 3 and 12 were firstly recovered from fungal genus Aspergillus. Compound 5 remarkable inhibited proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes, with IC50 of 12.11 ± 0.11 μM and 62.66 ± 0.80 μM, respectively. Meanwhile, the chemotaxonomic relations of isolated compounds and Aspergillus species were also discussed. © 2020 Elsevier Ltd