Plant-based by-products apply to a wide variety of sources. The definition of plant by-products includes morphological parts of plants like leaves, stems, roots, inflorescences, and already processed plant materials waste. For example, fruit, vegetables and nuts pomace after juice, wine, oils or plant beverage production. Also, spent grains from the grain industry, e.g., oat beverages production or beer industry. By-products are great carbon and nitrogen sources with high nutrient value for various fermentation technologies. Together with multistep enzyme-assisted extraction methods, it can achieve great results for creating higher-value food products and ingredients for food, nutraceutical, medical and material industries. The chapter introduces the main enzyme-assistance and fermentation using microbial strains technologies applicable to by-products in the food industry. It introduces future perspectives of different morphological parts of plant materials, which are not commonly used in production but have high perspectives. Moreover, the metabolomics of various plant materials fermentation is still scarce but evolving fast in the academic press. Interestingly, applications usually involve not one microbial strain but a symbiosis of mixed-culture populations. For example, sea buckthorn leaves after enzymatic hydrolysis are a great source for mesophilic lactic acid bacteria growth including Streptococcus thermophilus. The topic highly aligns with the upcycled foods category. Also, it implements United Nations Sustainable Development Goal 12, Responsible Consumption and Production, which seeks to halve food loss and waste in food production. Approximately 36.4 million tons of brewers spent grains, and 4–5 million metric tons of fruit and vegetable waste are produced annually. It invites the implementation of circular economy principles into production and has higher application to recycle valuable side streams. Plant cell traps various components, which in regular consumption are unavailable due to cellulolytic matrices. Implementing enzymatic reactions and fermentation processes, bioactive, and shorter chain macro components can have beneficial outcomes. Phytochemicals may have anti-inflammatory, anti-bacterial, and anti-virus properties, and prebiotic potential. Understanding these activities are essential to seek in nowadays holistic health awareness. Moreover, fermented extracts may also be an economically friendly part of greener synthesis applications for various polymeric materials and medical device development. However, with positive results, some challenges may occur, for example, legislation, cytotoxicity, and overall quality and safety for desired applications. These topics will be discussed in the upcoming chapter.