The objective of this study was to identify the effect of different land uses in peri-urban agriculture on the soil properties. Soil health indicators were evaluated in the top 10 cm at five tilled agricultural sites involving different cropping systems and use of agrochemicals within the peri-urban agricultural areas of Yaounde, Cameroon, and compared with a native forest land. The experimental data showed that the selected indicators were sensitive to cropping practice. Most cropped land had significantly higher total C, available N and P concentrations, soil pH, electrical conductivity, salinity, biomass C and P, dehydrogenase, beta-glucosidase, and acid phosphatase activities. Land producing corn (Zea mays L.) and sugarcane (Saccharum officinarum L.) differed from that producing tomatoes (Lycopersicon esculentum Mill.), but cultivation of these crops has significantly impacted native soil quality. However, phenol oxidase, microbal biomass C/organic C (C(mic)/C(org)), and microbial biomass C/microbial biomass P (C(mic)/P(mic)) were negatively affected. These appeared to be more consistent indicators of negative management causing changes to soil health and may be suitable for an early appraisal of soil health.