Objectives We aimed to assess the polypharmacy effect on appetite and malnutrition risk among Lebanese nursing home residents. We hypothesized that polypharmacy will be associated to lower appetite and increased of malnutrition. Methods A cross-sectional pilot study was carried out in two nursing homes in the North-Lebanon region. Fifty-three older adults (OA) aged 60 and above were recruited and were interviewed face-to-face. A general questionnaire was administered to gather information about their socio-demographics, dietary habits and physical activity routine. Appetite was evaluated by the Simplified Nutritional Appetite Questionnaire (SNAQ) validated for use with nursing homes residents. The participants' nutritional status was assessed using the Short Form of the Mini-Nutritional Assessment (MNA-SF). Polypharmacy was determined if OA were taking 5 or more medications. Information about attitudes towards the use, the number and the cost of medications was also collected. Differences in SNAQ and MNA scores based on polypharmacy were tested using Independent t-tests. Logistic regression was performed to assess the association between polypharmacy and nutritional status after adjusting for several factors. Results Our sample constituted of 49.1% females with an average age of 67.6 ± 3.8 and BMI of 22.3 ± 1.7 kg/m2. The majority were widowed (79.2%) and had a low level of education (85% elementary education). Regarding the MNA scores, 33% had a normal nutritional status while 59% were at risk of malnutrition and 8% were malnourished, with an average MNA score of 10.1 ± 2.2. The average SNAQ score was 11.0 ± 3.3, with 85% scoring ≤14, indicating an significant risk of at least 5% weight loss withing 6 months. Regarding medication use, 50.9% of OA take at least 5 drugs/d with an average of 4.3 ± 2 drugs. Independent t-tests showed that MNA scores were significantly lower in those taking 5 drugs/d vs those taking less (9.4 ± 2.5 vs 10.8 ± 1.6, P = .024) while no significant difference was observed for SNAQ scores (10.3 ± 2.9 vs 11.6 ± 3.6, P = .13). Logistic regressions did not show any significant association between polypharmacy and MNA or SNAQ categories. Conclusions Lower MNA scores were observed in OA taking ≥5 drugs/d indicating a higher risk of malnutrition with polypharmacy. This is significant since malnutrition can further worsen the aging process. Funding Sources N/A.