Two large missiles or bombs exploded in Gadhafi's Bab Al-Aziziya compound just after midnight, lightly wounding four people, according to a security guard at the site who spoke on condition of anonymity.
Gadhafi's whereabouts at the time of the attack were unclear.
The two bombs badly damaged a multi-story building and a second structure was damaged by that blasts. The second building apparently was used for more ceremonial purposes: Sofas and chandeliers and picture frames that had been knocked to the ground could be seen amid the rubble.
Early in the campaign against Gadhafi last month, a cruise missile blasted an administration building in the same complex, knocking down half the three-story building.
In Washingto on Sunday, three members of the Senate Armed Services Committee said that more should be done to drive Gadhafi out of power, including targeting his inner circle with air strikes. Gadhafi "needs to wake up every day wondering, `Will this be my last?'" Sen. Lindsey Graham, a Republican on the committee, told CNN's "State of the Union."
Monday's attack came a day after Gadhafi's forces unleashed a barrage of shells and rockets at Misrata in an especially bloody weekend that left at least 32 dead and dozens wounded. The battle for Misrata, which has claimed hundreds of lives in the past two months, has become the focal point of Libya's armed rebellion against Gadhafi since fighting elsewhere is deadlocked.