The present investigation has been carried out to study some clinical aspects and protein profile of malaria infected individuals in some coastal pockets of Tamil Nadu, India. The survey of malarial cases in the coastal areas of Thanjavur, Nagapattinam and Cudallore districts indicated 42 male and 30 female positive cases out of 120 samples collected from September 2007 to November 2009. The maximum number (29) malarial cases were observed in Cudallore than Thanjavur (24) and Nagapattinam (19) districts. The samples contain only two species of parasites namely Plasmodium falciparum and P. vivax in different stages in the smears of malarial positive cases. Among 72 malarial cases, 46 P. falciparum and 26 P. vivax were identified. The erythrocyte sedimentation rate was significantly decreased in malarial infected individual as compared with normal. The total leucocyte count was significantly higher in malaria infected individuals than normal. Similarly protein, aspartate amino transferase, alanine amino transferase and alkaline phosphatase were found to be higher in the malarial infected individuals than normal. Several protein bands were observed on 1st, 2nd, 5th, 7th, 14th and 21st day samples, but the 14th day sample was especially under taken in present study, because they formed more numbers of unique bands. Therefore, the slab gel was used for further target studies of protein profile. The 51 kDa protein was eluted from the gel for sequencing and structural analysis by various computational approaches using SOPMA, Ramachandran Plot, BLAST and Rasmol Model. The 51 kDa protein was detected as membrane receptor associated protein of the parasite. Thus, the present study provides the baseline information to the future researchers involved in the development of vaccines and paves the way for the control of malarial parasites using vaccine.