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Twenty-one compounds, including five new agarofuran sesquiterpenes, reissantins A−E (1−5), were isolated from Reissantia buchananii by means of bioassay-directed fractionation and their structures identified from spectral data. Reissantins A−C are the first reported simple agarofuran sesquiterpenes to contain a 5-carboxy-N-methyl-2-pyridone (CNMP) substituent, which has previously been found only in macroring agarofuran pyridine alkaloids. The major terpenoid components, celastrol (6) and its methyl ester derivative, pristimerin (7), were significantly active against nine cancer cell lines, including A549, MCF-7, HCT-8, KB, KB-VIN, U-87-MG, PC-3, 1A9, and PTX10 cell lines, with ED₅₀ values ranging from 0.076 to 0.34 μg/mL.