Disease has always been a great topic of concern in aquaculture industry. Antibiotic sensitivity, bacterial resistance is an issue that needs to be considered while treating the disease. Various steps were taken to find out possible alternative methods to minimize the antibiotics use in the aquaculture industry for disease management. Probiotics, feed additive and natural products such as herbals, sea weeds and good management practices in disease control have proposed for better production without having adverse effect. In the present study, five different Vibrio spp. isolated from four different marine fishes Strongylura spp (V1, V5), Sphyraena spp (V2), Lethrinus spp (V3), Carangoides spp (V4) are characterized by Random Amplification of Polymorphic DNA (RAPD) profile. Three primers (TW-3, RBA- 5, OPA-2) were used to distinguish Vibrio spp. by the RAPD profile analysis method. Among three primers RBA-5 showed fewer banding patterns range from 250 bp to 1000 bp. RAPD profiles were clearly distinctive between the five Vibrio isolates (V1-V5). Primer TW-3 and OPA-2 produced greater banding patterns between five Vibrio spp. The antibacterial activities of five important seaweeds namely Sargassum wightii, were screened against five different Vibrio spp isolated from commercially important marine fishes. The zone of inhibition in the crude extract of seaweeds (Sargassum wightii, Caulerpa peltata) was varied from against Vibrio spp. methanol extract of sea weeds shows maximum zone of inhibition against V3 strain and minimum zone of inhibition against V5 strain. The results clearly indicate that the seaweed compounds effectively inhibit the Vibrio spp.