Aflatoxin B1 (AFB1) is a pre-carcinogenic molecule produced by toxigenic fungi and is widely harmful to public health. Algae extracts are sub-cellular pilot plants rich in bioactive substances that aid detoxification. This study aimed to reduce AFB1-toxicity in biological tissues of administrated rats using two algae extracts, Spirulina (SPR) and Amphora (AMR). Algae extracts were prepared using an aqueous system, concentrated, and lyophilized before being administrated to rats. The extract contents of total phenolic and flavonoids were determined to indicate their bioactive content and antioxidant potency. The animal experiment was designed in 8 groups as the control negative and control positive (AFB1; 20 μg/kg BW/day); groups 3 and 4 were designed for control positive of algae applied at high doses for toxicity evaluation. Otherwise, four groups were classified as G5 and G6 for rats administrated by AFB1, followed by 50 and 100 mg/kg Spirulina extract, respectively. The G7 and G8 were administrated with an AFB1 dose followed by amphora treatment at 50 and 100 mg extract/kg, respectively. The results showed a significant content of algae extracts of phenolic compounds (27.36 ± 1.75 and 39.55 ± 1.14 mg GAE/g DW for the SPR and AMR, respectively), with a valuable antioxidant activity. For rats treated only with the SPR or AMR extracts, no tissue changes were recorded for the liver, kidney, pancreas, or testis. Again, the biochemical parameters of these groups are recorded without harmful impacts, particularly for the tumor markers of AFP, TNF-α, CEA, and ALP. Once more, a higher extract concentration was more effective in AFB1-toxicity reduction, particularly for the SPR on the liver and kidney tissues. The SPR extract manifested a protective impact in sensitive tissue against the AFB1 effect, particularly in the testis. The results recommend the application of SPR extract at 100 mg/kg bw as an effective treatment for AFB1-toxicity regulation (as pharmaceutical or nutraceutical) involved in daily habits.