Background The influenza virus can cause seasonal infections with mild to severe symptoms, circulating worldwide, and it can affect people in any age group. Therefore, this infection is a serious public health problem that causes severe illness and death in high-risk populations. Every year, 0.5% of the world’s population is infected by this pathogen. This percentage can increase up to ten times during pandemics. Influenza vaccination is the most effective way to prevent disease. In addition, anti-influenza drugs are essential for prophylactic and therapeutic interventions. The oseltamivir (OST, a neuraminidase inhibitor) is the primary antiviral used in clinics during outbreaks. However, OST resistant viruses may emerge naturally or due to antiviral pressure, with a prevalence of 1–2% worldwide. Thus, the search for new anti-influenza drugs is extremely important. Currently, several groups have been developing studies describing the biotechnological potential of microalgae and cyanobacteria, including antiviral activity of their extracts. In Brazil, this potential is poorly known and explored. Methods With the aim of increasing the knowledge on this topic, 38 extracts from microalgae and cyanobacteria isolated from marine and freshwater biomes in Brazil were tested against: cellular toxicity; OST-sensitive and resistant influenza replications; and neuraminidase activity. Results For this purpose, Madin-Darby Canine Kidney (MDCK)-infected cells were treated with 200 μg/mL of each extract. A total of 17 extracts (45%) inhibited influenza A replication, with seven of them resulting in more than 80% inhibition. Moreover, functional assays performed with viral neuraminidase revealed two extracts (from Leptolyngbya sp. and Chlorellaceae) with IC50 mean