Eight new bis-styryllactones, goniolanceolatins A-H (<b>1</b>-<b>8</b>), possessing a rare α,β-unsaturated δ-lactone moiety with a (6<i>S</i>)-configuration, were isolated from the CH<sub>2</sub>Cl<sub>2</sub> extract of the stembark and roots of <i>Goniothalamus lanceolatus</i> Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds <b>2</b> and <b>4</b> showed cytotoxicity, with IC<sub>50</sub> values ranging from 2.3 to 4.2 μM, and were inactive toward human noncancerous lung and colorectal cells. Compounds <b>1</b>, <b>3</b>, <b>6</b>, <b>7</b>, and <b>8</b> showed moderate to weak cytotoxicity. Docking studies of compounds <b>2</b> and <b>4</b> showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.