With the growing global demand for organically and biodynamically grown fireweeds, little research is being conducted on them, and little is known about how the different growing systems and the process of solid-phase fermentation changes biologically active substances and antioxidant activity. Our experiment was conducted in 2022 in Jonava district, Safarkos village, Giedres Nacevicienes organic farm (No. SER-T-19-00910, Lithuania, 55°00′22″ N 24°12′22″ E). This study aimed to investigate the influence of various growing systems (natural, organic, and biodynamic) and technological parameters (different duration: 24, 48 and 72 h) of aerobic solid-phase fermentation on the change of flavonoids, phenolic acids, tannins, carotenoids, chlorophylls, and antioxidant activity. High-performance liquid chromatography (HPLC) for polyphenols, carotenoids, and chlorophylls as well as the spectrophotometric method for antioxidant activity determinations were used. The results of the study showed that different growing systems (natural, organic, and biodynamic) and solid-phase fermentation had a significant effect on the quantitative composition of biologically active substances in the leaves of the fireweeds. According to these data, it would be possible to recommend fermented fireweed leaves grown organically as a source of polyphenols (especially: phenolic acids and flavonoids), leaves grown biodynamically as a source of carotenoids (exceptionally: lutein and beta-carotene) and chlorophyll, and leaves grown naturally for better antioxidant activity.