Background: Innovative treatments for lung cancer patients have significantly improved their lives. Therefore, patients who develop brain metastases are more likely to require management of quality of life (QoL) by reducing pathological decline in brain function. New therapeutic strategies have allowed us to manage brain metastases, thanks to the ability to cross the blood–brain barrier. Moreover, new molecules have been designed as adjuvants to standard treatments for the management of cancer patients with brain metastases. Methods: We implemented a descriptive, observational, retrospective study. Therefore, we consecutively collected the data of eighty-six (N = 86) patients admitted to our department (April 2020–April 2025) diagnosed with brain involvement in a thoracic neoplasm and treated with silibinin, in association with standard treatment. The main endpoint of our analysis is to define the safety profile of silibinin and to evaluate its eventual benefits in terms of QoL. Results: Silibinin was well tolerated (only one mild adverse event was reported); furthermore, patients taking silibinin had a good quality of life that was maintained over a long period of time, and in some cases, an improvement in neurological symptoms and overall patient well-being was also documented. Conclusions: Our study is the first collection of a large number of lung cancer patients with brain metastasis taking silibinin, which is very well tolerated and allows patients to maintain a good QoL.