The current surplus of lactose has promoted global research efforts seeking for alternate uses. Lactose presents technologically challenges such as low solubility and sweetness, as well as malabsorption by a certain population. There is a considerable industrial interest to further utilize lactose (LA) as a feedstock for the production of lactose-based ingredients. In this work, the catalytic conversion of LA to produce lactobionic acid (LBA) and lactulose (LAU) was studied. The reaction parameters of LA conversion were optimized in a continuous stirred tank reactor using a LA monohydrate solution over commercial ruthenium supported on activated carbon (5%-Ru/C). Then, the feasibility of the conversion of LA directly from sweet and acid whey permeate (SWP and AWP) was investigated under optimized catalytic reaction (stirring rate of 600 rpm, 60 bar oxygen pressure, and 70°C). The SWP was collected from a local cheese plant, while AWP was obtained from a Greek yogurt plant. Overall, the conversion of LA increased gradually within the reaction time. After 210 min, the values of LA conversion reached to 83.3, 36.2 and 33.4% for the LA solution, SWP, and AWP, respectively. Regardless of reaction time, the SWP showed the highest production yield of LA derivatives due to its high initial LA content (87.44 ± 4.93 g 100 g⁻¹ on dry matter) and higher pH level (6.23 ± 0.01). Furthermore, after 210 min catalytic reaction, LBA yield reached to its maximum values (4.99, 2.06, and 2.45% for SWP, AWP, and LA solution, respectively). During 30 min, the LAU yield reached to highest value (22.99, 15.28, and 17.91%, for SWP, AWP, and LA solution, respectively). Prolonged reaction time may induce degradation of produced derivate. Moreover, the acidic nature of LA solution and AWP did not favor formation of LAU. These results revealed that chemical conversion of LA can be a promising approach for the simultaneously production of LBA and LAU directly from the whey stream.