Two new fusicoccane diterpenes hypoestenonols A (1) and B (2), along with two known compounds verticillarone (3) and hypoestenone (4) were isolated from the n-hexane fraction of the methanolic extract of the aerial parts of Hypoestes forskalei (Acanthaceae) growing in Saudi Arabia. The structures were established by UV, IR, HRESIMS, 1D (1H and 13C NMR) and 2D (1H–1H COSY, HSQC, HMBC, and NOESY) NMR experiments, in addition to comparison with literature data. The total MeOH extract and isolated compounds were tested for their antiprotozoal and cytotoxic activities. The MeOH extract showed moderate activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei with IC50 values of 8.8, 8.1, 9.1 and 8.1 µg/mL without cytotoxicity (IC50 >64 µg/mL on MRC5 cells). A very weak in vitro antiplasmodial effect was observed for hypoestenonol A (1) (IC50 18.9 µM), verticillarone (3) (IC50 25.1 µM), and hypoestenone (4) (IC50 16.7 µM).