Colorectal cancer (CRC) represents one of the most serious health issues and the third most commonly diagnosed cancer worldwide. However, the treatment options for CRC are associated with adverse reactions, and in some cases, resistance can develop. Flavonoids have emerged as promising alternatives for CRC prevention and therapy due to their multitude of biological properties and ability to target distinct processes involved in CRC pathogenesis. Their innate disadvantageous properties (e.g., low solubility and stability, reduced bioavailability, and lack of tumor specificity) have delayed the potential inclusion of flavonoids in CRC treatment regimens but have hastened the design of nanopharmaceuticals comprising a flavonoid agent entrapped in a nanosized delivery platform that not only counteract these inconveniences but also provide an augmented therapeutic effect and an elevated safety profile by conferring a targeted action. Starting with a brief presentation of the pathological features of CRC and an overview of flavonoid classes, the present study comprehensively reviews the anti-CRC activity of different flavonoids from a mechanistic perspective while also portraying the latest discoveries made in the area of flavonoid-containing nanocarriers that have proved efficient in CRC management. This review concludes by showcasing future perspectives for the advancement of flavonoids and flavonoid-based nanopharmaceuticals in CRC research.