The effect of drilling waste on urease activities and substrate-induced respiration in wetland soil of Niger Delta of Nigeria was investigated, using Fadama, mangrove and meander soils respectively. Urease activity and substrate-induced respiration (SIR) were measured after 1, 7, 14, 28, 42, 56, 70, 105 and 140 days of incubation to evaluate the effects of drilling waste on soil biochemical perimeters. Results obtained indicated that Fadama soil urease activities varied from 13.5 to 2.10 mg NH4 – Hg-1 dry soil in drilling waste. Mangrove soil varied from 13.5 to 2.22 mg NH4 – Ng-1 dry soil in drilling waste. Meander soil activities varied from 14.7 to 3.10 mg NH4 – Ng-1 dry soil in drilling waste. Also, the substrate-induced respiration in Fadama and mangrove soil range from 2.05 to 0.05 ml CO2 kg-1 24 h-1 in drilling waste respectively. Analysis of enzyme activities indicated positive relationship between urease activities and SIR (r = 0.78, p < 0.05 Fadama (r = 1, P < 0.05 Mangrove) and (r = 0.83, P < 0.05 Meander). There was also a positive relationship between 5%, 10% and 15% treatment levels in Fadama, meander and mangrove soils.