Background In Mexico, there is an ancestral custom about the knowledge of the medicinal use of plants. Bixa orellana L. is a plant species that represents one of the main crops used in traditional medicine in southeastern Mexico. Background studies on its biological properties have been conducted on accessions harvested in Conkal, Yucatan, Mexico. Objectives In this work, the idea was to perform a phytochemical analysis of methanolic extracts of B. orellana. Materials and Methods Phytochemical screening was performed on methanolic extracts of leaves and seeds from two accessions of B. orellana, as well as on their antioxidant and antiproliferative activities. Results The phytochemical screening of the methanolic extracts of the leaves revealed the presence of tannins, terpenes, and saponins. A higher total content of phenols and flavonoids in leaves was also found compared to seeds, which coincides with a higher antioxidant activity in leaves compared to seeds. Regarding antiproliferative activity, the seeds and leaves of accession 3 showed the best results. Conclusion Accession 3 has better bioactive properties and can be a candidate in the search for antiproliferative and antioxidant compounds; this is the first study that associates this plant with this activity and demonstrates the chemical differences that exist between the accessions of B. orellana.