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Phytochemical investigation of <i>Artocarpus chama</i> stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (<b>1</b>), 3-(hydroxyprenyl) isoetin (<b>2</b>), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (<b>3</b>), and five known compounds, namely homoeriodictyol (<b>4</b>), isocycloartobilo-xanthone (<b>5</b>), artocarpanone (<b>6</b>), naringenin (<b>7</b>), and artocarpin (<b>8</b>). From the screening result, <i>A. chama</i> extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC₅₀ of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds <b>3</b>, <b>4</b>, <b>5</b>, <b>6</b>, and <b>8</b> showed strong activity against <i>Staphylococcus epidermidis</i>, <i>S. aureus</i>, methicillin-resistant <i>S. aureus</i>, and <i>Cutibacterium acnes</i>. This study is the first report on phytochemical investigation with new compounds and biological activities of <i>A. chama</i>. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms.