Zoonotic diseases pose a significant health challenge at the human-wildlife interface, especially in Sub-Saharan Africa where ecosystem services contribute significantly to local livelihoods and individual well-being. In Uganda, the fragmented forests of Hoima district, form part of a "biodiversity and emerging infectious disease hotspot" composed of communities with high dependency on these wildlife protected areas, unaware of the associated health risks. We conducted a cross-sectional mixed methods study from March to May 2017 and interviewed 370 respondents, using a semi-structured questionnaire from eight villages neighbouring forest fragments in Hoima District, Uganda. Additionally, a total of ten (10) focus group discussions (FGDs) consisting of 6-10 men or women were conducted to further explore the drivers of hunting and perception of zoonotic disease risks at community level. Qualitative and quantitative data were analysed using content analysis and STATA version 12 respectively. We found twenty-nine percent (29.0%, CI: 24.4-33.9) of respondents were engaged in hunting of wildlife such as chimpanzee (Pan troglodytes) and 45.8% (CI: 40.6-51.0), cane rats (Thryonomyidae spp). Acquisition of animal protein was among the main reasons why communities hunt (55.3%, CI: 50.1-60.4), followed by "cultural" and "medicinal" uses of wildlife and or its parts (22.7%, CI: 18.6-27.4). Results further revealed that hunting and bushmeat consumption is persistent for other perceived reasons like; bushmeat strengthens the body, helps mothers recover faster after delivery, boosts one's immunity and hunting is exercise for the body. However, respondents reported falling sick after consumption of bushmeat at least once (7.9%, CI: 5.3-11.1), with 5.3% (CI: 2.60-9.60) reporting similar symptoms among some family members. Generally, few respondents (37.0%, CI: 32.1-42.2) were aware of diseases transmissible from wildlife to humans, although 88.7% (CI: 85.0-92.0) had heard of Ebola or Marburg without context. Hunting non-human primate poses a health risk compared to edible rats (cane rats) and wild ruminants (cOR = 0.4, 95% CI = 0.1-0.9) and (cOR = 0.7, 95% CI = 0.2-2.1) respectively. Study suggests some of the pathways for zoonotic disease spillover to humans exist at interface areas driven by livelihoods, nutrition and cultural needs. This study offers opportunities for a comprehensive risk communication and health education strategy for communities living at the interface of wildlife and human interactions.