Water resources are the national wealth of each state, an important natural resource, and determine the development opportunities of most sectors of the economic complex of Ukraine. The Southern Bug River is the largest river, the basin of which is completely located in Ukraine. Due to the intensive growth of anthropogenic impact on the studied reservoir and the economic use of its resources, the quality of water in it has significantly decreased. To improve the quality of water in rivers, it is optimal to use biotechnological methods, which provide many opportunities for effective solutions to issues related to monitoring, assessment, and treatment of polluted watercourses. The aim of our study was to assess water safety, the current ecological status of the Southern Bug River within the Khmelnytsky region in three areas (Maryanivske Reservoir, Kopystyn, Shchedrivske Reservoir) and use in domestic needs, with analysis of potential risks to human health, development of new biotechnological and improvement of existing measures to improve water supply. The experimental part of the work was performed on the basis of the Khmelnytsky Regional Department of Water Resources in the laboratory at the address Khmelnytsky, st. Soborna, 29. We conducted a chemical assessment of the Southern Bug River on three indicators: salt composition (I1), tropho-saprobiological (I2), and specific toxic substances (I3). Research of river waters was carried out in order to control the MPC (maximum permissible concentrations) of substances for use in household and food needs of the population and to propose biotechnological methods of river water purification within the Khmelnytsky region. According to our research on hydrochemical characteristics, the water contained elevated levels of NH4, NO2, NO3, PO4, the average values of HSC (chemical oxygen demand) exceeded the MPC in all areas by 2 to 5 times. This may be due to exposure to organic compounds of natural origin. The content of nitrites, nitrates is within normal limits, but the content of ammonium salt exceeds the MPC up to 20 times in the village Kopystyn and from 2 to 7 times in the village of Letychiv. According to many indicators of the salt block, the maximum concentration limit was not exceeded, except for the village Kopystyn, the concentration of Magnesium (Mg) was 84.33 mg/dm3 at a rate of 40.00 mg/dm3. According to specific toxic substances, the water belonged to the III class 4 quality category, Chromium (Cr) was not detected, Manganese (Mn) and Copper (Cu) were within normal limits, although the Copper content was high. The concentration of Iron (Fe) varies in different areas and during the year, there is a case of excess Iron in the village. Kopistin up to 0.86 mg/dm3 at a rate of 0.30 mg/dm3. Iron affects the intensity of phytoplankton development and the qualitative composition of the microflora, so its concentration is subject to seasonal fluctuations. To improve the quality of water in the Southern Bug River, we have proposed the use of biotechnological methods, including those that provide many opportunities to effectively address issues related to monitoring, assessment, and treatment of polluted watercourses.