A Novel series of sulphonamide schiff base compounds obtained from sulfa drugs were synthesized by the reaction of 2,4-dichloro-5-sulfamoylbenzoic acid with aldehydes. The synthesized compounds were characterized by using FT-IR, Mass, 1H NMR and 13C NMR spectroscopy to confirm the chemical structures of synthesized compounds. The sulphonamide Schiff base compounds were tested for anti-bacterial, anti-fungal and anti-malarial evaluation. The biological activity of synthesized compounds was evaluated by assessing the inhibitory concentration (IC) by measuring their inhibition zone versus certain kinds of standard antibiotics. Noticeably, compound NV5 was the most potent compound in-vitro anti-microbial (S. aureus) with a MTCC value of 96 microgram/ml in comparison with Ampicillin and compounds NV9 and NV11 showed good activity in-vitro anti-fungal (C. albicans) with a MTCC value of 277 microgram/ml. Similarly, compound NV6 showed high potent activity of anti-malarial (P. falciparum) with mean IC50 value as compared to other synthesized derivatives. Addition to this, two of selected compounds showed liquid crystalline properties.