Despite growing awareness of the health risks associated with climate change, how Nepalese people perceive these threats and their links to diarrheal diseases remains insufficiently understood in Nepal. This study examines and compares knowledge of climate change and diarrheal prevention practices among communities in four districts in Koshi and Karnali provinces. We conducted a cross-sectional study from February 12 to June 28, 2023, surveying 882 households using a structured questionnaire. Data were collected on socio-demographic characteristics, climate change knowledge, perception of climate change and its impact on diarrhea, and practices for diarrhea prevention. Statistical comparisons between Koshi and Karnali provinces were performed to identify potential drivers of differences, and multiple logistic regression analyses were used to examine associations between socio-demographic factors and study outcomes, including climate knowledge and diarrheal prevention practices. Of the 882 participants, 70% were aware of climate change; among them, 66.1% strongly believed climate change increases diarrheal risk, with higher agreement in Koshi (P = 0.029); 60.9% linked rising temperatures to more diarrheal cases (P = 0.046), while only 24% associated it with increased precipitation. Regarding diarrheal prevention, 94.3% reported access to safe drinking water and 84.1% used improved sanitation facilities (P = 0.001). Only 11.3% of participants were vaccinated against rotavirus; 36.6% did not purify their water and 37.2% used cloth-filtered water. Despite access to care, 70.1% delayed treatment for diarrheal illness, varying by province (P < 0.001). In the multivariate analysis, females had significantly higher odds of lacking knowledge of climate change compared with males (AOR: 1.51; 95% CI: 1.14-2.08). A similar pattern was observed among participants engaged in agriculture (AOR: 6.16; 95% CI: 1.42-26.50) and labor occupations (AOR: 9.48; 95% CI: 1.81-49.71), indicating lower knowledge levels in these groups. Residents of the Karnali Province (AOR: 2.59; 95% CI: 1.83-3.66) had higher odds of not immediately visiting a health institution for diarrheal illness, indicating delayed healthcare-seeking behavior. Although two-thirds of participants recognized the impact of climate change on diarrheal disease, our study identified low rotavirus vaccination coverage, suboptimal household water treatment practices, delayed care seeking, and limited recognition of rainfall as a risk factor. These findings highlight the need to strengthen education on climate-related risk factors, promote safe water and sanitation practices, and encourage timely healthcare seeking in the study districts to combat diarrhea in the context of climate change.