In an interview with the BBC, Mr Obama said it was “distressing” not to have made progress on the issue “even in the face of repeated mass killings”.
He vowed to keep trying, but the BBC’s North America editor Jon Sopel said the president did not sound very confident.
However, Mr Obama said race relations had improved during his presidency.
Hours after the interview, a gunman opened fire at a cinema in the US state of Louisiana, killing two people and injuring several others before shooting himself.
In a wide-ranging interview, President Obama also said:
 The UK must stay in the EU to have influence on the world stage
 He is confident the Iran nuclear deal will be passed by Congress
 Syria needs a political solution in order to defeat the Islamic State group
 He would speak “bluntly” against corruption and human rights violations in Kenya
 He would defend his advocacy of gay rights following protests in Kenya
 Despite racial tensions, the US is becoming more diverse and more tolerant
Read the full transcript of his interview
Mr Obama lands in Kenya later on Friday for his first visit since becoming president.
But with just 18 months left in power, he said gun control was the area where he has been “most frustrated and most stymied” since coming to power in 2009.
“If you look at the number of Americans killed since 9/11 by terrorism, it’s less than 100. If you look at the number that have been killed by gun violence, it’s in the tens of thousands,” Mr Obama said.