Among the diversity of microorganisms, the rarest and least explored are microorganisms that live in conditions of high oxygen in the environment and can experience the effects of natural oxidative stress. Here we suggest that the actinobacteria of Lake Baikal, sampled in the littoral zone, may produce natural products with antioxidant activity. The current study aimed to assess the effects of experimentally increased amounts of oxygen and ozone on the morphology of actinobacteria, DNA mutations, and antioxidant potential. In this experiment, we cultivated actinobacteria in liquid culture under conditions of natural aeration and increased concentrations of dissolved oxygen and ozone. Over a period of three months, bacterial samples were collected every week for further analysis. Morphological changes were assessed using the Gram method. A search for DNA mutations was conducted for the highly conserved 16S rRNA gene. The evaluation of antioxidant activity was performed using the DPPH test. The biotechnological potential was evaluated using high-resolution liquid chromatography-mass spectrometry approaches supplemented with the dereplication of natural products. We demonstrated the synthesis of at least five natural products by the Streptomyces sp. strain only under conditions of increased oxygen and ozone levels. Additionally, we showed morphological changes in Streptomyces sp. and nucleotide mutations in Rhodococcus sp. exposed to increased concentrations of dissolved oxygen and oxidative stress. Consequently, we demonstrated that an increased concentration of oxygen can influence Lake Baikal actinobacteria.