Diabetic foot complications represent a significant public health challenge in Cameroon, often resulting in severe morbidity and amputation. While clinical management has been extensively studied, limited attention has been paid to informal caregivers supporting patients outside hospital settings. This study investigates the correlation between knowledge, perception, and challenges faced by primary caregivers of diabetic foot patients at Buea and Limbe Regional Hospitals. A cross-sectional quantitative design was employed, utilizing a structured questionnaire distributed to 100 caregivers. Data were analyzed using descriptive statistics, chi-square tests, and Pearson correlation to identify relationships among the variables. Findings revealed that 45% of respondents had good knowledge of diabetic foot care, and a significant positive correlation was observed between knowledge levels and positive perception (r = 0.62, p < 0.01). Financial burden, lack of training, emotional stress, and time constraints emerged as the most prevalent caregiving challenges, which negatively impacted caregiver perceptions. The study contributes to understanding caregiver dynamics in diabetic foot management and highlights the need for educational interventions, financial and psychosocial support systems, and caregiver-inclusive policy frameworks. This research expands the discourse on chronic disease management by centering caregivers as key health actors and proposes actionable recommendations for institutional and policy-level change. Addressing the challenges and enhancing the capacities of caregivers can lead to better patient outcomes and reduce the burden of diabetic foot complications in resource-limited settings.