Angiogenesis plays a crucial role in malignant tumor progression and development. The present study aimed to identify lead plants with selective anti-angiogenic properties. A total of 26 methanolic extracts obtained from 18 plants growing in Saudi Arabia and Jordan that belong to the Lamiaceae family were screened for their cytotoxic and anti-angiogenic activities using MTT and rat aortic ring assays, respectively. Four novel extracts of Thymbra capitata (L.) Cav., Phlomis viscosa Poir, Salvia samuelssonii Rech.f., and Premna resinosa (Hochst.) Schauer were identified for their selective anti-angiogenic effects. These extracts did not exhibit cytotoxic effects on human endothelial cells (EA.hy926) indicating the involvement of indirect anti-angiogenic mechanisms. The active extracts are potential candidates for further phytochemical and mechanistic studies.