This study examines the performance, combustion, and emissions characteristics of a single-cylinder internal combustion diesel engine when fueled with a blend of diesel and biodiesel derived from muskmelon seeds. The kinematic viscosity of the extracted muskmelon seed oil was 6.1 cSt at 40 °C, which is higher than the kinematic viscosity of petroleum diesel of 2.6 cSt. Muskmelon biodiesel was further analyzed using thin-layer chromatography (TLC) and high-voltage separator tests. A comparison of the fuel properties of muskmelon biodiesel with conventional diesel fuel revealed that muskmelon biodiesel could be used alone or in a diesel–biodiesel blend to fuel compression diesel engines. In this study, muskmelon seed biodiesel was blended with diesel fuel at proportions of 10 %, 20 %, and 50 % (BD10, BD20, and BD50, respectively). At a relatively low rotational speed of 1200 rpm, the brake thermal efficiency (BTE) of the engine operated with BD10 and BD20 blends were 36.1 % and 36.0 %, respectively, while the brake-specific fuel consumption (BSFC) of the two blends were 0.260 kg/kWh, and 0.262 kg/kWh, respectively. These values closely resemble those typically observed in diesel fuel engines. Indeed, the average BTE of the BD20 blend was only 3.24 % less than the average BTE of diesel fuel. Diesel fuel generates less NOx and SO2 emissions compared to biodiesel blends: BD100 emitted the most NOx pollution of all fuels tested. In addition, BD10 released significantly more SO2 emissions compared to the other fuels tested. However, the BD20 blend outperformed all other blends in terms of CO, NOx, and SO2 emissions at high engine speeds. The only exception was H2S emissions, which were higher than BD50 and BD100. BD20 also exhibited significantly reduced CO emissions compared to diesel fuel, while BD10 emitted significantly more CO emissions than the other biodiesel blends. Our findings revealed that BD20 exhibited the best engine performance and lower emissions among all fuels tested. In other words, BD20 is the ideal fuel blend for use in diesel engines and does not require any alterations to the engine. Muskmelon waste seeds represent a non-edible waste stream that can be exploited in the production of biodiesel fuel, allowing for the upcycling of a potentially problematic thermochemical conversion feedstock. This potentially valuable use for waste muskmelon seeds in the energy sector could address the wastefulness associated with this particular waste stream.