Studies on the Effects of Man’s Activities on the Natural Ecosystem and Biotechnological Solutions in restoring the ecosystem have been conducted. The Obanliku L.G.A of Cross River State, Nigeria, was chosen for the study because of its unique ecology, and practical demonstration of ignorance of the people in the region, in dealing with the ecological systems. The study shows that bush burning is a common practice of the people as a clearing strategy for agricultural purposes, and very often the wild fire goes beyond the farmers’ control destroying the ecosystem, and gases such as carbon dioxide, carbon monoxide are emitted into the environment. These gases destroy the ozone layer which protects the environment, plants and animals from the direct effects of the sun. Fishing activities on river ‘Orieh,’(a meandering river that stretches over 60km and empties into the Atlantic ocean), is done with the unprofessional method of using chemicals such as gamelin 20, vitox 85, and aldrin powder, that result to massive death of aquatic organisms and ignorantly to enhance harvest of the aquatic animals. Deforestation for: timber, domestic energy, agricultural and constructional purposes is done without control, resulting to loss of endanger species, properties, global warming, with its associated sea level rise and flooding due to melting of the polar ice. Waste from agricultural activities, plastics, electronic devices, human waste (faeces) and oil spills resulting from subsurface exploitation and exploration failures, activities of vandals and transportation accidents have devastating consequences on the environment and human health. Mechanical clearing of farm lands should be encouraged as the biomas derived from clearing can be used for generating bio-energy and environmentally friendly fertilizers as compared to the inorganic fertilizer. Selective fishing strategies should be adopted, such as the use of nets, where the young fishes are returned back to the river. Government should put enabling laws in place to guide the extinction of endangered flora and fauna. Plants are known to be totipotent, thus, biotechnology is the ultimate solution to: Aggressive Reforestation and aforestation, organic waste recycling technologies, such as the generation of bio-energy from the biomass, the use of deoxyribonucleic acid (DNA) bar-coding to guard against illegal exploitation of game reserves, like transformed elephant tusk, genetic engineering to produce drought and disease resistant hybrid that will withstand adverse environmental conditions, and bio-sensors that will dictate areas that have been contaminated with crude oil spills. Regular medical checkup on the people and environmental awareness programs should be done in schools and religious gatherings. Indicators of a depleted environment includes the following: Global temperature rise, flooding, poor air quality, poor ground water quality, poor soil fertility, outbreaks of epidemics and pandemics, extinction of flora and fauna.