Background: Athamanta sicula L., a member of Apiaceae, is an annual perennial herb and it is known in Sicilian popular medicine with the name of "spaccapietre" (rock splitters), because fresh roots infusions are indicated as diuretic and used in the treatment of diseases of the urinary tract, and to dissolve kidney stones. Materials and Methods: Acetone extracts of leaves, flowers, and stems of A. sicula L. were investigated in vitro for antibacterial and cytotoxic activities. Antimicrobial activity was carried out against bacterial and fungal strains and antiproliferative activity against a group of human cancer cell lines (K-562, NCI-H460, and MCF-7). Results: All acetone extracts, apiol and myristicin, resulted inactive as antimicrobial agents at the maximum tested concentration of 200 μg/mL, but they induced significant antiproliferative activity on the tested cancer cell lines. Conclusions: Our study show that both apiol and myristicin could be tested as novel treatment in cancer chemotherapy.