Three undescribed hybrid flavan-chalcones, caesalpinflavans D-F, and an unreported normonoterpene-chalcone heterodimer, caesalpinnone B, along with three known biflavonoids were isolated from the twigs and leaves of Caesalpinia digyna. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Caesalpinflavan F was identified as a bis-(hybrid flavan-chalcone), its natural occurrence was supported by HPLC-IT-TOF-MS analysis. The condensation of caesalpinflavan B with acetone was possibly a key step in the biosynthesis of caesalpinflavan F. Caesalpinnone B represents an unprecedented meroterpenoid featuring a cyclobutane central framework, which was derived from chalcone and normonoterpenoid via a key [2 + 2] cyclization reaction. Biological evaluation revealed that compounds caesalpinflavan D, oxytrodiflavanone A, and caesalpinnone B exhibited moderate cytotoxicity against HL-60, SMMC-7721, SW480, A-549 and/or MDA-MB-231 cell lines with IC₅₀ values ranging from 8.051 ± 0.673 to 24.26 ± 0.61 μM. This study provided evidence for further research and possible utilization of C. digyna in the future.