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Three new polyene compounds, talacyanols A–C (<b>1</b>–<b>3</b>), along with two known compounds, ramulosin (<b>4</b>) and eurothiocin A (<b>5</b>), were isolated from the marine fungus <i>Talaromyces cyanescens</i> derived from a seaweed <i>Caulerpa</i> sp. Structures of <b>1</b>–<b>5</b> were established by one-dimensional and two-dimensional (1D/2D) NMR, HR-ESIMS, and the modified Mosher’s methods, as well as comparison with previously reported literature data. All the compounds (<b>1</b>–<b>5</b>) were tested for their in vitro cytotoxic and anti-neuroinflammatory activities. Among them, <b>1</b> showed moderate cytotoxic activity against a panel of cancer cell lines (HCT-15, NUGC-3, NCI-H23, ACHN, PC-3, and MDA-MB-231) with GI₅₀ values ranging from 44.4 to 91.6 μM, whereas compounds <b>2</b> and <b>5</b> exhibited anti-neuroinflammatory effect without cytotoxicity against all the tested cell lines.