Silver Bullets are, as the name implies, bullets made of silver. They are often used in folklore as an effective weapon against werewolves and other monsters. They are featured in The Wolf Among Us as one of Bigby's only weaknesses, and have an unlockable Book of Fables entry. Bloody Mary fires one into Bigby at the end of "A Crooked Mile", nearly killing him, and in "Cry Wolf" he finds several of them being produced at Sheppard Metalworks.
Book of Fables Entry
The legends of great and magical wolves often make mention of their weakness against weapons made of silver. And those tales bear out to be true. The silver bullet Mary shot Bigby with was not the first. But any of them could be his last. Any silver left in Bigby's body weakens his system, slows his healing, and can cause long-term damage.