Objective: To determine the prevalence and antibiotic resistance of Escherichia coli (E.coli) , in seafood obtained from Cuddalore and Parangipettai fish landing centres. Also, to identify the susceptibility of E. coli against predominant seaweeds red alga Kappaphycusalvarezii (K. alvarezii) and brown alga Padina boergessenii (P. boergessenii) extracts as sulfated polysaccharides and polyphenols respectively. Methods: A total of 48 samples (Two stations Cuddalore and Parangipettai, Tamil Nadu, India). Sampling area are fish landing centre where fishes caught from sea and estuary, seafood processing plants (packing and ice packed fishes) and local fish markets (fish samples). After isolation totally 80 strains were analyzed for its antimicrobial resistance and sensitivity against commercially 10 antibiotics. The ampicillin resistant E. coli CE21 was identified through molecular techniques as 16S rDNA sequencing. Two seaweeds K. alvarezii and P. boergessenii were screened for antibacterial activity against 12 antibiotic resistant E. coli strains. Results: Totally 48 swabbed samples from two different fish handling area were characterized for total bacterial and E. coli count. Mostly, the E. coli strains were isolated from fish local market and seafood processing plants before and after packaging process. In that maximum 56.25% strains were resistant to ampicillin and the minimum 2.5% strains were resistant to chloramphenicol. Therefore, the E. coli CE21 was identified through molecular techniques E. coli (GenBank accession number GU065251), The MIC value for polyphenol extract was slightly less than sulfated polysaccharides. E. coli strain isolated from Parangipettai was considerably increased MIC value that Cuddalore. Conclusions:The polyphenol and sulfated polysaccharides showed promising inhibitory response against all antimicrobial resistant E. coli strains and in particular the inhibitory response of ampicillin resistant E. coli.