Tuberculosis constitutes today a serious threat to human health worldwide, aggravated by the increasing number of identified multi-drug resistant strains of Mycobacterium tuberculosis (Mtb), its causative agent, as well as by the lack of development of novel mycobactericidal compounds for the last few decades. A novel series of benzofuran-3-carbohydrazide and its analogs was synthesized and characterized spectroscopically. All the compounds were characterized and screened for in vitro anti-tuberculosis (anti-TB) activity against Mycobacterium tuberculosis H37Rv strains by using resazurin assay utilizing microtiter-plate method (REMA). These compounds also showed good antifungal activity against Candida albicans. Thus, the high level of activity shown by the compounds (8a, 8k) suggests that these compounds could serve as leads for development of novel synthetic compounds with enhanced anti-TB and antifungal activity.