As a kind of renewable and high oxygen content fuel, polyoxymethylene dimethyl ether (PODE) can be added in diesel to realize energy saving and emissions reduction. To evaluate the combustion and emission characteristics of a diesel engine fueled with diesel and diesel/PODE mixtures, exhaust gas recirculation (EGR) and main-pilot injection strategies with various injection timings were applied. PODE was blended with diesel by volume to form mixtures which were marked as D100 (pure diesel), D90P10 (90% diesel + 10% PODE), and D80P20 (80% diesel + 20% PODE). The results showed that the ignition delay (ID) and combustion duration (CD) of D80P20 were the shortest because of the highest cetane number (CN) and high oxygen content of PODE, indicating more concentrated heat release. At low and medium loads, D80P20 achieved the highest peak heat release ratio (PHRR) and peak combustion temperature (PCT) among the three fuels, and it was 14.3% and 3.6% higher than those of D100. PODE blending with diesel can significantly reduce particulate matter (PM) and D80P20 has the lowest PM emissions at all loads. Compared with D100, both PM and nitrogen oxide (NOx) emissions of PODE blends decreased simultaneously with 20% EGR at all loads. With the increase of pilot-main interval, the ID and CD of all test fuels increased, while the NOx and PM emissions decreased. The conclusions of the present research provide a state of the application in light-duty engines fueled with diesel/PODE blends in future work.