Several head-to-head and head-to-tail dimers of piplartine (1a) were prepared, and the configurations of the resulting truxillic and truxinic acid derivatives were established by a combination of NMR experiments and single-crystal X-ray analysis. Their cytotoxic activity was screened in photometric sulforhodamine B assays. All of these dimers showed a decreased cytotoxicity compared to 1a except for the β-truxinic acid derivative 3a. For this unprecedented head-to-head dimer high cytotoxic activity was established against several human tumor cell lines, and IC50 values as low as 1.1 μM were found.