Six lactone derivatives, including four α‐pyrones derivatives (1–4), two α‐furanone derivatives (5 and 6), were isolated from the Dendrobium pendulum. Structural elucidation of these undescribed lactone derivatives were accomplished on the basis of detailed nuclear magnetic resonance analysis, and the absolute configurations of compounds 1–4 were confirmed by electronic circular dichroism (ECD) techniques. The cytotoxic effects of isolated compounds on human breast cancer cell MDA‐MB‐231 were evaluated by the MTT assay. [ABSTRACT FROM AUTHOR]