A survey was carried out to investigate the knowledge, perception and interest of secondary school students about biotechnology. A total of 334 questionnaires were distributed to students in Senior Secondary 3 classes from eight secondary schools within Calabar metropolis. Data was collected and analyzed using SPSS version 7.5. Results revealed 105 (34.21%) of students had limited knowledge of medical biotechnology, genetic engineering and genetically modified products. 91 (30.03%) of the students agreed that biotechnology is the use of living organisms to produce goods and services while 102 (33.41%) accepted that biotechnology is a new technology based on biology 62 (20.39%) were willing to embrace the applications of biotechnology. 152 (50.03%) do not agree that biotech will improve services for mankind; 90 (29.51) had no idea about the applications of biotechnology; 31 (10.24%) students disagreed that cloning results in perfectly identical individuals while the highest positive responses; 92 (30.31%) was recorded for questions regarding in vitro fertilization. The students also showed a very low interest 76 (25%) in pursuing biotechnology as a degree in the University. Generally students' knowledge, perception, and interest in Biotechnology were low among Secondary School students in Calabar. There is a need to immediately increase enlightenment and emphasis on the applications of biotechnology among Secondary school students to enable them appreciate the benefits of biotechnology.