The spermatogenesis is a precisely-timed cellular proliferation that takes place in the seminiferous tubules of testes and is meticulously regulated by gonadotrophins, androgens and temperature. Hormonal, nonhormonal and thermal methods of male contraception have been researched with success; though a clinically viable method is yet to evolve. Testicular sperm lack motility and fertilizing ability, which they gain during their transit through the long epididymal conduit whose distal end serves as a store house of mature sperm in a quiescent state, ready for ejaculation during coitus. Epididymal maturation has been a target for male contraceptive research to avert interruptions of fundamental testicular functions like spermatogenesis and steroidogenesis. However, several experimental successes have not yet yielded a practicable method of fertility regulation. Coitus culminates in the propulsion of epididymal sperm within seconds through the vas deferens into the female vagina and marks the initiation of sperm motility, a vigorous physical activity that is crucial for fertilization. Highly motile spermatozoa have a brief stay in the vagina before starting their ascent in the female reproductive tract. Vaginal spermatozoa have been targeted for contraception since ages. Spermicides and sperm immobilizers inactivate sperm immediately on deposition in the vagina, while they are placed in a rather ‘ex-vivo’ condition outside the body. Their need based usage, minimal systemic involvement; easy application, self-controlled reversibility and potential capability to obliterate sexually transmitted infections add significant value to contraception. We have reviewed here our recent endeavors in this important area of chemical contraception by using designed chemical synthesis approach to inhibit spermatozoa and infection.